cssi/SciSciGPT-SciSciNet huggingface dataset:
Practical considerations for using K3 cameras in CDS mode for high-resolution and high-throughput single particle cryo-EM.

Abstract Detector technology plays a pivotal role in high-resolution and high-throughput cryo-EM structure determination. Compared with the first-generation, single-electron counting direct detection camera (Gatan K2), the latest K3 camera is faster, larger, and now offers a correlated-double sampling mode (CDS). Importantly this results in a higher DQE and improved throughput compared to its predecessor. In this study, we focused on optimizing camera data collection parameters for daily use within a cryo-EM facility and explored the balance between throughput and resolution. In total, eight data sets of murine heavy-chain apoferritin were collected at different dose rates and magnifications, using 9-hole image shift data collection strategies. The performance of the camera was characterized by the quality of the resultant 3D reconstructions. Our results demonstrated that the Gatan K3 operating in CDS mode outperformed standard (nonCDS) mode in terms of reconstruction resolution in all tested conditions with 8 electrons per pixel per second being the optimal dose rate. At low magnification (64kx) we were able to achieve reconstruction resolutions of 149% of the physical Nyquist limit (1.8 A with a 1.346 A physical pixel size). Low magnification allows more particles to be collected per image, aiding analysis of heterogeneous samples requiring large data sets. At moderate magnification (105kx, 0.834 A physical pixel size) we achieved a resolution of 1.65 A within 8-h of data collection, a condition optimal for achieving high-resolution on well behaved samples. Our results also show that for an optimal sample like apoferritin, one can achieve better than 2.5 A resolution with 5 min of data collection. Together, our studies validate the most efficient ways of imaging protein complexes using the K3 direct detector and will greatly benefit the cryo-EM community.
Discovery of COVID-19 Inhibitors Targeting the SARS-CoV2 Nsp13 Helicase

The raging COVID-19 pandemic caused by SARS-CoV2 has infected millions of people and killed several hundred thousand patients worldwide. Currently, there are no effective drugs or vaccines available for treating coronavirus infections. In this study, we have focused on the SARS-CoV2 helicase (Nsp13), which is critical for viral replication and the most conserved non-structural protein within the coronavirus family. Using homology modeling and molecular dynamics approaches, we generated structural models of the SARS-CoV2 helicase in its apo- and ATP/RNA-bound conformations. We performed virtual screening of ~970,000 chemical compounds against the ATP binding site to identify potential inhibitors. Herein, we report docking hits of approved human drugs targeting the ATP binding site. Importantly, two of our top drug hits have significant activity in inhibiting purified recombinant SARS-CoV-2 helicase, providing hope that these drugs can be potentially repurposed for the treatment of COVID-19.
Bioorthogonal Hydroamination of Push-Pull-Activated Linear Alkynes.

A bioorthogonal reaction between N,N -dialkylhydroxylamines and push-pull-activated halogenated alkynes is described. We explore the use of rehybridization effects in activating alkynes, and we show that electronic effects, when competing stereoelectronic and inductive factors are properly balanced, sufficiently activate a linear alkyne in the uncatalyzed conjugative retro-Cope elimination reaction while adequately protecting it against cellular nucleophiles. This design preserves the low steric profile of an alkyne and pairs it with a comparably unobtrusive hydroxylamine. The kinetics are on par with those of the fastest strain-promoted azide-alkyne cycloaddition reactions, the products regioselectively formed, the components sufficiently stable and easily installed, and the reaction suitable for cellular labeling.
Phenome to Genome – Application of GWAS to Asthmatic Lung Biomarker Gene Variants

We utilize the GWAS Catalog to gather a set of common SNPs with high magnitude odds ratio values for an increased risk of asthmatic phenotypes. After collecting a set of SNPs, we parse it down to a subset of ten representative variations. Using the odds ratio and known prevalence of asthma in the population, we then calculate each SNP’s individual contribution towards the lifetime genetic risk of developing asthma. For a hypothetical European patient, we estimate that the SNP from our set with the smallest odds ratio value sees an increase of lifetime risk by 8%, while the SNP with the largest odds ratio value causes the risk of developing asthma to more than double. For a more complete and accurate prediction of asthma risk, additional work must be done to incorporate the contribution from less common SNP and SNPs with lower odds ratios, along with other risk factors, including age, gender, lifestyle habits, and environmental influences.
An Implicit Analytical Surface Potential Based Model for Long Channel Symmetric Double-Gate MOSFETs Accounting for Oxide and Interface Trapped Charges

Abstract We present analytical models for calculating surface potential for both undoped (intrinsic) and doped (extrinsic) long channel symmetric double-gate MOSFETs. Starting with Poisson’s equation, we derive the implicit surface potential equation(s) for the symmetric double-gate MOSFET in the accumulation and depletion/inversion regions of operation. This results in a continuous surface potential curve throughout all operating regions of the device. By introducing a defect potential to surface potential equations for the symmetric double-gate MOSFET, the models add the effects of oxide-trapped charge and interface traps (both uniform and non-uniform distributions) that can build up in the gate dielectric of the device. A drain current model is presented for both the undoped and doped cases of the SDG MOSFET. The accuracy of the surface potential analytical models and drain current models are validated by comparing to numerical results from two dimensional TCAD simulations.
Equipment-based Pilates reduces work-related chronic low back pain and disability: A pilot study

Summary Objective This study investigated effectiveness of an equipment-based Pilates protocol for reducing pain and disability in individuals with work-related chronic low back pain (CLBP). Methods Twelve workers with non-specific CLBP participated in a quasi-experimental, one-group, pretest-posttest pilot study of supervised 6-week equipment-based Pilates exercise. Pain severity was assessed using a 100-mm visual analog scale (VAS). Physical function was assessed using the Oswestry disability index (ODI). Results The Pilates intervention significantly reduced pain (mean decrease in VAS 30.75 ± 20.27, p p Conclusions Rehabilitative Pilates exercise reduced pain and disability in workers with CLBP. Further research is needed to investigate Pilates exercise for rehabilitation of work-related injuries in large populations.
Instruction in Letter-Sound Correspondences for Children With Autism and Limited Speech:

This study used a multiple probe across participants’ research design to evaluate the effects of instruction on the acquisition of letter-sound correspondences (LSCs) by three young children with autism spectrum disorder and limited speech. All three children (ages 3–5 years) reached criterion for identifying the LSCs targeted during instruction, and a Nonoverlap of All Pairs (NAP) analysis showed evidence of medium to strong treatment effects. All three children also provided evidence of maintenance and generalization of LSC skills to other tasks. Implications for instruction and future research directions are discussed.
Mixed-Mode Multicomputers with Load Adaptability

Dynamically reconfigurable mixed-mode computers are those systems that can be configured at run-time into Multiple SIMD and MIMD autonomous submachines. Therefore, they are also known as MSIMD/MIMD computers. In the existing MSIMD/MIMD architectures, the role of a processor to run as either a processing element “PE” or a control unit “CU”, is fixed at design time. It will be shown that such static assignment adversely affects the system's flexibility and performance. This paper introduces an MSIMD/MIMD architecture with dynamic processors assignments. Unlike the existing machines, this architecture dynamically configures/reconfigures each processor to run as either a PE or a CU as needed. A cost-efficient dynamically reconfigurable hardware is provided in order to establish a broadcasting link between any CU and its PEs in an SIMD submachine. It will be shown that the proposed architecture offers significantly better performance/cost ratio than the existing comparables.
Radiation Dose Planning, Computer-Aided

Radiation therapy aims at delivering a desired radiation dose to the intended volume while limiting the dose to surrounding healthy tissues as much as possible. The purpose of treatment planning is to design treatment strategies to best achieve such goals, and to estimate the radiation dose throughout the irradiated volume before the start of the treatment. Thanks to the rapid developments in computer and medical imaging technologies, treatment planning can now be done efficiently under the guidance of the patient’s internal anatomy in three dimensions, incorporating possibly functional and metabolic information with ever increasing resolution and clarity. This article reviews key components in the computer-aided radiation dose planning, including virtual simulation, image registration, three-dimensional dose calculation, treatment plan optimization, and treatment plan evaluation, emphasizing specifically the impact of computer technology on these recent developments. As we are ascending into an era of image-guided radiation therapy with computer-controlled delivery and real-time image guidance and feedback, advanced computer technology will play an ever increasingly significant role in radiation oncology. Keywords: radiation therapy planning; virtual simulation; digitally reconstructed radiograph; image registration; intensity modulation; treatment plan optimization; inverse planning; dose calculation; computer-controlled delivery
Photolabeling of the 6 and 10 S conformations of gizzard myosin with 3'(2')-O-(4-Benzoyl)benzoyl-ATP. Proline 324 is near the active site.

3'(2')-O-(4-Benzoyl)benzoyl-ATP (Bz2ATP) was used as a photoaffinity label of the ATP binding site of unphosphorylated chicken gizzard myosin. Specific photolabeling of the active site of 6 S myosin was assured by forming a stable myosin.Co(II)Bz2ADP.orthovanadate complex (termed trapping) prior to irradiation. Co2+ was used in place of Mg2+ to prevent the known photoreaction of vanadate with myosin which destabilizes the trapped complex. [3H] Bz2ADP.Pi was also stably trapped on gizzard myosin by forming the 10 S folded conformation of the protein in the presence of [3H]Bz2ATP and Mg2+. Irradiation of 6 S myosin containing orthovanadate trapped [3H] Bz2ADP or 10 S trapped [3H]Bz2ADP.Pi gave 32 and 30% covalent incorporation, respectively. The 50-kDa and precursor 68-kDa tryptic peptides of the subfragment-1 heavy chain derived from both forms of myosin were found to contain essentially all of the covalently attached [3H]Bz2ADP. Parallel experiments with untrapped [3H]Bz2ADP showed extensive nonspecific labeling of all of the major tryptic peptides and the light chains. Eight labeled peptides, isolated from 6 and 10 S photolabeled myosin, contained the sequence G319-H-V-P-I-X-A-Q326, where X corresponds to labeled proline 324. [14C]Bz2ADP was previously shown to label serine 324 in skeletal subfragment-1 (Mahmood, R., Elzinga, M., and Yount, R. G. (1989) Biochemistry 28, 3989-3995), which corresponds to alanine 325 in the gizzard sequence. Thus, this region of the 50-kDa tryptic fragment, near the nucleotide binding site, in both skeletal and smooth muscle myosins, must fold in essentially the same manner.
Factors Influencing Students to Enroll in Health Information Management Programs

This nonexperimental quantitative descriptive-correlative research study was performed to describe the sources with the greatest influence on the participants’ decision to enroll in a postsecondary educational program with the intent of working toward a career in health information management. Participants were asked, “Which sources have the greatest influence on an individual's decision to enroll in a postsecondary educational program with the intent of working toward a career in health information management (HIM)?” The study population was composed of matriculated students enrolled in accredited postsecondary schools offering an undergraduate medical billing and coding program at a brick-and-mortar campus in a two-county area of a South Atlantic state. The study found that an environmental source, specifically career job opportunities, was statistically significant as the greatest source of influence for these participants. This research aims to support efforts to provide the health information management subsector of the healthcare industry with a sufficient number of trained professionals to fill the identified need for trained HIM professionals, particularly medical coding specialists.
Transneuronal Circuit Analysis with Pseudorabies Viruses

Over the past decade there has been a dramatic increase in the use of viruses as transneuronal tracers of neuronal circuitry. The method exploits the propensity of neurotropic viruses to invade neurons and then produce infectious progeny that cross synapses to infect other neurons within a circuit. The protocols and commentaries included in this unit focus upon the use of the swine alpha herpesvirus known as pseudorabies virus (PRV) for polysynaptic analysis. Here, the aspects of experimental design that have the greatest import for successful use of viruses in circuit definition are presented. Accordingly, the protocols included in this unit can be applied in concert with methods in which the use of classical tract tracers has been detailed. A procedure for retrograde infection of CNS circuits in the rat CNS by peripheral injection of virus is detailed, while transneuronal analysis by intracerebral injection is also described. A variant of these procedures, transneuronal analysis with multiple recombinant strains, is also described along with methods for growing and titering viral stocks, and procedures for single and dual immunohistochemical localization of viral antigens in fixed brain tissue.
Management of Pediatric Migraine Headache in the Emergency Room and Infusion Center

Migraine is a common disorder that starts at an early age and takes a variable pattern from intermittent to chronic headache with several exacerbations throughout a lifetime. Children and adolescents are significantly affected. If an acute headache is not aborted by outpatient migraine therapy, it often causes severe disability, preventing the child from attending school and social events. Treating the acute severe headache aggressively helps prevent prolonged disability as well as possible chronification. Multiple medications are available, mostly for the outpatient management of an attack and include the use of over-the-counter anti-inflammatory medications as well as prescribed medications in the triptan group. These therapies do sometime fail and the exacerbation can last from days to weeks. If the headache lasts 72 hours or longer it will fall in the category of status migrainosus. Status migrainosus is described as a severe disabling headache lasting 72 hours or more by the ICHD3 criteria. Disability is a major issue in children and adolescents and aggressive acute measures are to be taken to control it as soon as possible. Early aggressive intravenous therapy can be very effective in breaking the attack and allowing the child to be quickly back to normal functioning. This article reviews what is available for the treatment of pediatric primary headaches in the emergency room.
Localized nighttime D-region disturbances and ELF propagation

Abstract ELF radio wave propagation measurements at northeastern U.S. sites within 1600 km of the U.S. Navy test transmitter in Wisconsin occasionally display an unexpected early-morning null behavior in which a decrease of more than 6 dB in signal strength occurs over a period of several hours. These severe ELF disturbances occur only occasionally during the several days following magnetic storms when similar, but less pronounced behavior is found to coincide with phase disturbances on VLF paths across the northern U.S. These disturbances appear to be caused by energetic electrons precipitated into middle latitudes from the radiation belt. The magnitude of the severe ELF disturbances requires an explanation involving a twofold discontinuity in the Earth-Ionosphere waveguide. It is suggested that the effective ionosphere reflecting height is lowered immediately to the east of the receiving locations by particulate bombardment but then is raised further east at the geomagnetic conjugate of the South Atlantic anomaly, beyond which quasi-trapped particles are no longer available at lower D -region heights.
Game theory for security: Key algorithmic principles, deployed systems, lessons learned

Security is a critical concern around the world. In many security domains, limited security resources prevent full security coverage at all times; instead, these limited resources must be scheduled, avoiding schedule predictability, while simultaneously taking into account different target priorities, the responses of the adversaries to the security posture and potential uncertainty over adversary types. Computational game theory can help design such unpredictable security schedules. Indeed, casting the problem as a Bayesian Stackelberg game, we have developed new algorithms that are now deployed over multiple years in multiple applications for security scheduling. These applications are leading to real-world use-inspired research in the emerging research area of “security games” specifically, the research challenges posed by these applications include scaling up security games to large-scale problems, handling significant adversarial uncertainty, dealing with bounded rationality of human adversaries, and other interdisciplinary challenges.
General Stability Analysis of Orthotropic Sandwich Panels for four Different Boundary Conditions (Extension of the March-Ericksen Approach)

This work contains a general stability analysis of orthotropic sandwich panels including a revised formulation of the March-Ericksen energy method as well as the more exact differential equation method. Certain special cases are formulated using the revised March-Ericksen method and some approximations applicable to this method are indicated. Buckling coefficient curves are plotted for various boundary conditions using the energy method. The appendices give a detailed derivation of the differential equations of the problem and a solution of these equations for the buckling coefficient of a simply-supported panel. Diese Arbeit enthalt eine allgemeine Untersuchung der Stabilitat von orthotropen Sandwich-Platten, die sowohl eine revidierte Formulierung der March-Eriksenschen Energiemethode als auch der genaueren Differentialgleichungsmethode einschliest. Gewisse spezielle Falle werden mit Hilfe der revidierten March-Ericksenschen Methode behandelt, und auf einige darauf anwendbare Naherungen wird hingewiesen. Fur verschiedene Randbedingungen werden unter Verwendung der Energiemethode Beulkoeffizienten-Kurven aufgezeichnet. Im Anhang werden eine eingehende Ableitung der Differentialgleichungen des Problems und eine Losung dieser Gleichungen fur den Beulkoeffizienten einer frei drehbar gelagerten Platte gegeben.
Drivers of Surgery for the Degenerative Hip, Knee, and Spine: A Systematic Review

Background Surgical treatment for degenerative conditions of the hip, knee, and spine has an impact on overall healthcare spending. Surgical rates have increased dramatically and considerable regional variation has been observed. The reasons behind these increasing rates and variation across regions have not been well elucidated.
Transient, sparsely-populated compact states of apo and calcium-loaded calmodulin probed by paramagnetic relaxation enhancement: interplay of conformational selection and induced fit

Calmodulin (CaM) is the universal calcium sensor in eukaryotes, regulating the function of numerous proteins. Crystallography and NMR show that free CaM-4Ca2+ exists in an extended conformation wit...
Beating the memory drum: Rapid sequential visual presentation (RSVP) on a 4K PDP-8

A program for presenting alphanumeric strings in rapid succession on a Videoterminal is described. Rates of up to 30 items/sec can be obtained with relatively “slow” systems by creating a push-up stack in the terminal’s display memory and scrolling the items past a small display window during presentation. Advantages of such a program are discussed, and the system is compared to mechanical techniques of rapid sequential visual presentation.
Cytomegalovirus: Detection in human colonic and circulating mononuclear cells in association with gastrointestinal disease

The specificity and strength of the reported association between cytomegalovirus (CMV) and colonic adenocarcinoma were tested by analysis of a consecutive series of surgically resected colons for: CMV-DNA by a DNA-DNA reassociation kinetics (hybridization) procedure; latent virus by co-cultivation of fresh tissue with indicator fibroblasts; and CMV viral antigens by immunofluorescence. Ten of 13 cancer patients whose colonic tissue was able to be examined by all techniques showed some evidence of active or prior CMV infection. Four cancer specimens were CMV-DNA (hybridization)-positive; an additional specimen from a cancerous colon was culture-positive. In six instances, CMV DNA was detected in mucosal cells adjacent to colon adenocarcinoma. In tissue from one of three patients with ulcerative colitis and two of seven patients with other non-neoplastic colonic disease, CMV DNA was also detected. No fresh colonic tissues were demonstrated to have CMV surface or nuclear antigens when examined by immunofluorescence. Culture of peripheral lymphocytes was positive for CMV in three of 14 cancer patients. A CMV-specific defect in humoral immunity could not be documented in that most cancer patients, as well as cancer-free patients, exhibited circulating specific antibody to CMV and had a normal capacity for CMV-specific antibody-dependent cellular cytotoxicity. We conclude that CMV, probably in a latent form, is readily detectable in colonic cells of man, including those derived from malignant, pre-malignant and non-malignant tissues. Neither preferential replication in damaged tissue nor carriage of CMV by peripheral lymphocytes homing to gut appear to explain the presence of CMV in colon cells.
Classical stability of a homogeneous, anisotropic inflating space-time

We study the classical stability of an anisotropic space-time seeded by a spacelike, fixed-norm, dynamical vector field in a vacuum-energy-dominated inflationary era. It serves as a model for breaking isotropy during the inflationary era. We find that, for a range of parameters, the linear differential equations for small perturbations about the background do not have a growing mode. We also examine the energy of fluctuations about this background in flat space. If the kinetic terms for the vector field do not take the form of a field strength tensor squared, then there is a negative energy mode and the background is unstable. For the case where the kinetic term is of the form of a field strength tensor squared, we show that classical solutions to the equations of motion that are close to the background solution have energy greater than or equal to zero. This suggests that the background is metastable.
Prolactin response to low-dose dexamethasone challenge in combat-exposed veterans with and without posttraumatic stress disorder and normal controls

The prolactin and cortisol responses to dexamethasone (0.5 mg) were studied in combat veterans with (n = 18) and without (n = 12) posttraumatic stress disorder (PTSD) and normal controls (n = 18). Both veteran groups demonstrated greater prolactin suppression than the normals. In contrast, only veterans with PTSD showed an enhanced cortisol suppression in response to dexamethasone. These findings suggest that the prolactin response to dexamethasone may reflect a feature of combat exposure rather than PTSD per se.
Hepatic fibrosis and survival in biliary atresia

In biliary atresia, progression of hepatic fibrosis before the Kasai portoenterostomy may explain why age is a major determinant of survival of the native liver. Blinded fibrosis scoring of surgical liver biopsies demonstrated that age and fibrosis correlate. Those biopsies with severe fibrosis predicted significantly worse survival.
Most-Probable-Number Technique for the Enumeration of Aromatic Degraders in Natural Environments

A most-probable-number (MPN) method is described for the enumeration of heterotrophic populations capable of utilizing chlorinated and nonchlorinated benzoates and phenols as sole carbon sources. A correlation coefficient of 0.91 was obtained between the numbers determined by the MPN technique and the standard plate count. The MPN method gave realistic cell counts when population densities were low, and the presence of oligocarbophiles did not give spurious results.
Statistical Theory of Many-Electron Systems. General Considerations Pertaining to the Thomas-Fermi Theory

The density matrix for a many-electron system has been examined with a view toward extending the statistical theory of Thomas and Fermi. The single-particle density matrix is expanded in terms of a power series in $\ensuremath{\hbar}$, according to a procedure developed here for operators consisting of a series of powers of the classical Hamiltonian, the zeroth-order terms corresponding to the Thomas-Fermi theory. Second-order terms in the expansion are identifiable in the expression for the energy: they correspond to exchange energy, the Weizs\"acker inhomogeneity correction for the kinetic energy and, possibly, correlation energy. Their presence follows from the expansion procedure, rather than from an a priori insertion into the theory.While the development here has been concerned mainly with the single-particle density function at the absolute zero of temperature, the procedure has been developed in sufficiently general terms to permit an evaluation to be made of the many-electron density matrix as a function of temperature.The results which have been obtained have been utilized to modify the theory of Fermi and Amaldi which has then been applied to the following atomic states: H ($^{2}S$), He ($^{1}S$), He ($^{3}S$), ${\mathrm{C}}^{++}$ ($^{1}S$), O ($^{1}S$). The disparity between the calculated energy for He ($^{3}S$) and the observed value is less than 6%, while for the remaining cases the disparity does not exceed 2.5%. The radial densities obtained correspond roughly to available quantum densities; they fail, however, to indicate any "shell-structure" nor to display the expected behavior for distances very close to, or very far from the atomic nucleus.
An alternative statistical procedure in evaluating applied research products

For decades, applied researchers have had a choice between statistical methods that have been shown to not be perfectly valid (null hypothesis significance testing procedure) or to be based on premises that are difficult to justify (Bayesian method). These limitations have slowed the progress of product development, particularly in safety research. We propose a new statistical method termed epistemic ratio procedure (ERP), which is both logically valid and based on accurate premises that can be generated by either consumers or designers. This procedure allows applied researchers to compare the degree of empirical support among competing products or services. Theoretical and methodological implications for future applied research are discussed.
Magnetostatic wave devices for UHF band applications

Magnetostatic surface wave (MSSW) devices made with pure and gallium-substituted yttrium-iron garnet (Ga:La-YIG) films are described. These devices include nondispersive and dispersive delay lines, band-pass filters, oscillators, and resonators. By controlling the magnitude of the bias magnetic field and the temperature of operation, it is possible to tune these devices over a wide frequency range extending from 0.3 to 4 GHz and from 3 to 18 GHz using Ga:La-YIG and pure YIG films, respectively.
E-cadherin in the mature and developing organ of Corti of the mouse.

The reticular lamina of the mammalian cochlea is formed by the tightly joined apical surfaces of hair cells and supporting cells. This lamina creates a barrier separating endolymph and perilymph, two fluids of different composition. The preservation of this fluid barrier is a requirement for cochlear function. This study aimed to determine whether the calcium-dependent, cell adhesion molecule, E-cadherin was appropriately placed both temporally and spatially to contribute to the formation and maintenance of the reticular lamina. Cochleas aged E15 to P31 were stained immunocytochemically for E-cadherin. In the P31 organ of Corti, E-cadherin is localized to the apical intercellular junctions of supporting cells, but is absent from supporting cell-hair cell borders. During development, E-cadherin is present only on the apices and lateral edges of those cells which will eventually lie adjacent to fluid spaces — pillar, outer hair and Deiters cells. The molecule disappears from the lateral cell membranes at about the time in development that fluid spaces form. These data suggest that E-cadherin plays a role in maintaining the reticular lamina by mediating inter-supporting cell adhesion and raise the possibility that fluid space opening in the organ of Corti is facilitated by the down-regulation or redistribution of E-cadherin.
Development and application of aluminum-boron composite material

Specific design studies of the application of aluminum-boron composites to structural components of the F-106 aircraft are presented and weight and performance improvements assessed. A summary of the current mechanical and physical properties, manufacturing, nondestructive test, and structural test evaluations of aluminum-boron are presented. Savings for components, which approach 50% in some cases, and the airframe weight saving for the F-106 are presented. The problems of high-temperature joining and cost of implementation are touched on briefly.
Effective Role of Hormonal Therapy in Metastatic Primary Neuroendocrine Breast Carcinoma

Primary neuroendocrine carcinoma (PNEC) of the breast is extremely rare.(1) Because of the rarity of this cancer, long-term prognosis, biologic behavior, and treatment are not well known. PNEC can have high expression of estrogen receptor (ER) and progesterone receptor (PR). It is important to differentiate PNEC of the breast from other metastatic diseases to the breast because of the differences in treatment. We herein report the successful treatment of a patient with PNEC of the breast and high expression of ER and PR by means of hormonal therapy.
Glucocorticoids Suppress Inflammation but Spare Innate Immune Responses in Airway Epithelium

Epithelial cells produce molecules that alter the growth and differentiation of mesenchymal cells, trigger the adhesion to endothelial cells and recruitment of inflammatory leukocytes, and regulate the activation of resident and infiltrating inflammatory cells. Recently, it has become clear that the airway epithelium also participates in innate immune responses. Accumulating evidence suggests that epithelial products such as complement, collectins, lysozyme, lactoferrin, secretory leukocyte protease inhibitor, and defensins can lead to localized destruction of microorganisms. While suppressing systemic adaptive immune responses, glucocorticoids exert little or no inhibitory effect on the ability of the epithelium to express these antimicrobial substances and, in some cases, may even elevate their production. Inhaled glucocorticoids generally profoundly inhibit epithelial cell expression of genes of inflammation, including chemokines, cytokines, and enzymes. Glucocorticoids may enhance the sensitivity of the epithelial surface to Toll-like receptor ligands, and they have been found to induce the expression of surfactant proteins A and D in several in vitro and in vivo model systems. Supporting the concept that glucocorticoids enhance innate immunity while suppressing adaptive immunity, these drugs enhance the survival and/or function of neutrophils and alveolar macrophages but induce the apoptosis of airway dendritic cells.
End connection effects on vortex shedding susceptibility of welded aluminum truss tubular web members

A series of experiments and analyses have been conducted to assess the vulnerability of hollow circular web members in welded aluminum sign truss structures to wind-induced resonant vibrations. Results from nondestructive field testing were used to develop and verify a reliable method for determining the fundamental natural frequency of vibration for various categories of truss web members (incorporating end connection fixity effects). These natural frequencies for different types, sizes, and lengths of web members were then related to their computed vortex-shedding frequencies, toward estimating the critical wind speeds for web member resonant vibration. Outcomes were correlated with wind-related fatigue damage observed in the field; simple design recommendations for preventing this sort of damage by limiting the maximum web member slenderness ratio have been developed.
Consistent low-field picture of bcc3He exchange

Consideration of a physically plausible potential for bcc solid3He suggests that there is significant antiferromagnetic pair exchange between next nearest neighbors and that triple exchange is less important than previously believed. Experimental consequences of such a thesis are consistent with all existing low magnetic field data.
Inhibiting phosphorylation of the oncogenic PAX3-FOXO1 reduces alveolar rhabdomyosarcoma phenotypes identifying novel therapy options

Patients with translocation-positive alveolar rhabdomyosarcoma (ARMS), an aggressive childhood tumor primarily characterized by the PAX3-FOXO1 oncogenic fusion protein, have a poor prognosis because of lack of therapies that specifically target ARMS tumors. This fact highlights the need for novel pharmaceutical interventions. Posttranslational modifications such as phosphorylation are becoming attractive biological targets for the development of such interventions. Along these lines, we demonstrated that PAX3-FOXO1 is phosphorylated at three specific sites and that its pattern of phosphorylation is altered relative to wild-type Pax3 throughout early myogenesis and in ARMS tumor cells. However, little work has been performed examining the effect of directly inhibiting phosphorylation at these sites on ARMS development. To address this gap in knowledge, we used small molecule inhibitors or mutational analysis to specifically inhibit phosphorylation of PAX3-FOXO1 to investigate how altering phosphorylation of the oncogenic fusion protein affects ARMS phenotypes. We found that inhibiting the phosphorylation of PAX3-FOXO1 at Ser201 significantly reduced migration, invasion and proliferation in two independent ARMS tumor cell lines. Further, we found that inhibition of phosphorylation at Ser205 also decreased proliferation and anchorage-independent growth. Consistent with these in vitro results, we demonstrate for the first time that PAX3-FOXO1 is phosphorylated at Ser201 and Ser205 in a primary tumor sample and in tumor cells actively invading the surrounding normal tissue. This report is the first to demonstrate that the direct inhibition of PAX3-FOXO1 phosphorylation reduces ARMS tumor phenotypes in vitro and that these phosphorylation events are present in primary human ARMS tumors and invading tumor cells. These results identify phosphorylation of PAX3-FOXO1, especially at Ser201, as a novel biological target that can be explored as a promising avenue for ARMS therapies.
On new approaches of assessing network vulnerability: hardness and approximation

Society relies heavily on its networked physical infrastructure and information systems. Accurately assessing the vulnerability of these systems against disruptive events is vital for planning and risk management. Existing approaches to vulnerability assessments of large-scale systems mainly focus on investigating inhomogeneous properties of the underlying graph elements. These measures and the associated heuristic solutions are limited in evaluating the vulnerability of large-scale network topologies. Furthermore, these approaches often fail to provide performance guarantees of the proposed solutions. In this paper, we propose a vulnerability measure, pairwise connectivity, and use it to formulate network vulnerability assessment as a graph-theoretical optimization problem, referred to as β-disruptor. The objective is to identify the minimum set of critical network elements, namely nodes and edges, whose removal results in a specific degradation of the network global pairwise connectivity. We prove the NP-completeness and inapproximability of this problem and propose an O(log n log log n) pseudo-approximation algorithm to computing the set of critical nodes and an O(log1.5n) pseudo-approximation algorithm for computing the set of critical edges. The results of an extensive simulation-based experiment show the feasibility of our proposed vulnerability assessment framework and the efficiency of the proposed approximation algorithms in comparison to other approaches.
Vertical transmission of Mycoplasma haemolamae in alpacas (Vicugna pacos)

Abstract The purpose of this study was to determine the frequency of vertical transmission of Mycoplasma haemolamae from dam to cria, whether colostral transmission of M. haemolamae occurs and provide preliminary data on colostral M. haemolamae specific antibody from pregnant alpacas on a farm with known prevalence of infection. M. haemolamae specific PCR was performed on blood and colostrum from pregnant alpacas and their cria ( n = 52 pairs). Indirect fluorescent antibody testing was performed on a subset ( n = 43) of the colostrum samples. Total immunoglobulin concentrations of colostrum and cria sera and M. haemolamae specific IgG (prior to and after ingesting colostrum) were determined by turbidometric immunoassay and indirect fluorescence antibody testing respectively. Sixteen of 52 dams (30.7%) pre-partum and one of 52 cria post-partum (1.9%; prior to ingesting colostrum) were PCR positive for M. haemolamae , while 36/52 dams (69%) and 51/52 cria (98%) tested negative for M. haemolamae by PCR. All 43 colostrum samples and 52 of 52 post-colostrum cria blood samples (100%) were negative by PCR. The dam giving birth to the M. haemolamae PCR positive cria was PCR negative. Statistically, it was no more likely for a PCR positive dam to give birth to a M. haemolamae , PCR positive cria (prior to colostrum ingestion) than a PCR negative dam ( p = 0.3077). M. haemolamae specific IgG was present in 22 of 43 (51%) of colostrum samples at a 1:10 dilution and 14 of 22 (64%) at a 1:100 dilution. There was no relationship between the PCR status of the dam and whether or not M. haemolamae specific antibodies were present in colostrum. Among the animals tested, in utero transmission of M. haemolamae was rare (1/52 pre-colostral alpaca cria), and all colostrum samples were negative for M. haemolamae by PCR. These data indicate that colostrum from positive dams is unlikely to harbor this parasite and therefore does not serve as a source of infection to newborn cria. Colostrum derived from both PCR positive and negative dams contained M. haemolamae specific antibodies. Our findings suggest that M. haemolamae specific antibodies may play a role in immunity to this hemoparasite; however, challenge studies are necessary to fully evaluate the role of M. haemolamae specific antibodies. Furthermore, antibody prevalence and detectable titers may provide different estimates than those available from current PCR based prevalence studies. Our findings also suggest that M. haemolamae isolates from geographically distinct regions do not differ significantly from each other.
Exploring stable pattern formation in models of tussock moth populations

1. The western tussock moth (Orgyia vetusta) at the University of California Bodega Marine Reserve (Sonoma County, California, USA) exhibits dense, localized populations in the midst of extensive habitats where variation in host plant quality or predator abundance is unable to explain the restricted extent of the outbreaks. 2. Two primary features suggest that the host patterning is intrinsically generated: (i) female tussock moths are wingless, producing a low effective dispersal distance for the hosts; and (ii) the tussock moth population is attacked by several species of widely dispersing wasp and fly parasitoids. 3. We consider a set of spatially explicit host–parasitoid models to examine whether intrinsically generated patterns are possible within this system. These models include a spatially extended Nicholson–Bailey model to examine general features of pattern formation in host–parasitoid systems, and two system-specific models, an individual-based simulation and a population-level analytic model, to examine the details of this empirical system. 4. Both stable patterning and rapid extinction of the host population are initial-condition dependent outcomes of the general and specific models, implying that an intrinsically generated stable host pattern is feasible within the tussock moth system. 5. Stable patterning is enhanced by a large parasitoid-to-host dispersal ratio, local host resource limitation, and increased parasitism at the host patch's edge.
Evaporation of solutes from water

Abstract A model is developed to define the evaporation rates of solutes from water. The rate equation, similar in form to the Knudsen equation, takes into consideration the effect of air and subwater turbulences on the evaporation loss. At given system conditions, the factor accounting for the air turbulence appears to be essentially constant and independent of temperature (3.5–25°C) for various organic chemicals and water. These characteristics allow one to study the rate of evaporation from water and the relative enhancement by subwater mixing for different solutes. This report shows that the volatilization loss of pure substances and solutes with low Henry's law constants is enhanced by air turbulence, not by subwater mixing. However, the loss of volatile solutes (high Henry's law constants) may be promoted both by air turbulence and by subwater mixing, in which the extent of enhancement by liquid mixing is determined primarily by the Henry's law constant. The present model provides a theoretical basis to explain these effects and others, which appear to be important for assessment of pollutant evaporative transport in the environment.
Synthesis and structure-activity studies of schweinfurthin B analogs: Evidence for the importance of a D-ring hydrogen bond donor in expression of differential cytotoxicity.

Abstract The synthesis and biological evaluation of several enantioenriched schweinfurthin B analogs were undertaken to develop structure–activity relationships and guide design of probes for their putative molecular target. The desired stilbenes contain a common left-half hexahydroxanthene ring system and an aromatic right-half with varied substituents. The synthesis involves penultimate Horner–Wadsworth–Emmons coupling of one of several right-half phosphonates with the aldehyde comprising the left-half of 3-deoxyschweinfurthin B. Preparation of the requisite phosphonates, and the respective stilbenes, as well as the cytotoxicity profiles of these new compounds in the National Cancer Institute’s 60 cell-line anticancer screen is described. Several of these analogs displayed cytotoxicity patterns well-correlated with the natural product and differences in activity of ∼10 3 across the various cell lines. Together, these assay results indicate the importance of at least one free phenol group on the aromatic D-ring of this system for differential cytotoxicity.
Molecular Papanicolaou tests in the twenty-first century: molecular analyses with fluid-based Papanicolaou technology.

Abstract Objective: This study was undertaken to demonstrate the feasibility of performing molecular analyses at the deoxyribonucleic acid, ribonucleic acid and protein levels of cervical cytologic examination with a methanol fluid-based Papanicolaou specimen collection system. Study Design: Genomic deoxyribonucleic acid and total ribonucleic acid were extracted from cell pellets obtained from the residual fluid-based Papanicolaou specimen collection buffer after clinical processing. Genomic and human papillomavirus deoxyribonucleic acid polymerase chain reaction and reverse transcriptase–polymerase chain reaction were performed. Messenger ribonucleic acid transcript analysis and human papillomavirus 16 E6 mutational analysis were also performed. Methylation-specific polymerase chain reaction was used to evaluate hypermethylation status of the p16 gene and the gene for E-cadherin. Immunohistochemical staining for protein expression was performed on the processed monolayer slides. Results: Cell pellets from the residual fluid-based cytologic specimen yielded good quality deoxyribonucleic acid and ribonucleic acid. Molecular analyses of genomic deoxyribonucleic acid were successful for the identification of human papillomavirus E6 and p53 polymorphism status by means of restriction enzyme digestion and direct sequencing. Methylation status of the promotor regions of the p16 tumor suppressor gene and the gene for E-cadherin were also successfully identified. Ribonucleic acid was used as the template for transcript analysis and mutational analysis of the corresponding complementary deoxyribonucleic acid of the p53 gene. Protein expression analysis was demonstrated by immunohistochemical staining for carcinoembryonic antigen. Conclusion: It is feasible to conduct multiple molecular analyses at the deoxyribonucleic acid, ribonucleic acid, and protein levels of the cervicovaginal cell pellets from the residual fluid-based Papanicolaou cytologic specimen. This relatively simple and widely used collection system will allow significant advances in molecular epidemiology and eventual development of a molecular Papanicolaou test. (Am J Obstet Gynecol 2000;183:39-45.)
Estimation of a Utility Function from Semen Purchases from Holstein Sires

Abstract Weighting of expected income versus risk of a decision maker is expressed by his utility function; it can be estimated by analyzing his portfolio selection. To estimate a utility function of dairymen, the portfolio selection was measured by semen purchases or expenditures by dairymen for semen of 328 Holstein sires of eight bull studs. Purchases were divided into those from technicians and direct. Three indexes combining Predicted Differences for milk, fat, and type were constructed to estimate gross income of dairymen. Income after subtracting semen price also was used for three additional indexes. Multiple regression analyses were used to estimate coefficients or weights of the utility function. The weight for expected income was significant for all indexes. Coefficients for risk (measured as variance of income) were highly significant for gross income indexes and one index after semen price was subtracted. These coefficients were significant when portfolio selection was measured by expenditures for total semen purchased and for semen purchased directly by dairymen and distributors. Coefficients were nonsignificant for purchases from technicians and for portfolio selection measured by units of semen purchased. Dairymen based their selection of semen mainly on expected income. A tendency towards risk aversion was observed.
A generalization of Ryser's theorem on term rank

In his work on classes of (0, 1)-matrices with given row and column sum vectors, Herbert Ryser proved that the maximum term rank possible in a normalized class, �, can be realized by a matrix having � (independent) 1's in positions (1, �), (2, � � 1), � , (�, 1). We study the positions occupied by sets of t � � independent 1's.