cssi/SciSciGPT-SciSciNet huggingface dataset:
Cis-Regulatory Differences Explaining Evolved Levels of Endometrial Invasibility in Eutherian Mammals

Eutherian (placental) mammals exhibit great differences in the degree of placental invasion into the maternal endometrium, with humans being on the most invasive end. Previously, we have shown that these differences in invasiveness is largely controlled by the stromal fibroblasts of the maternal endometrium, with secondary effect on stroma of other tissues resulting in correlated differences in cancer malignancy. Here, we present a statistical investigation of the second dogma linking the phenotypic and transcriptional differences to the genomic changes across species, revealing the regulatory genomic sequence differences underlying these inter-species differences. We show that gain or loss of specific transcription factor binding site sequences are connected to the inter-species gene-expression differences in a statistically significant manner, with a particularly larger effect on stromal genes related to invasibility. We also uncover transcriptional factors differentially regulating genes related to pro- and anti- invasible property of stroma. This work extends the understanding of inter-species differences in stromal invasion to the causal genomic sequence differences paving new avenues to target stromal characteristics to regulate placental, or cancer invasion.
Increased Vasoactive Inotrope Score Following Left Ventricular Assist Device Placement Is Associated With Increased Mortality And Early Right Ventricular Failure

Background The vasoactive inotrope score (VIS) has been used as a model to predict mortality and adverse events following left ventricular assist device (LVAD) implantation. We attempt to validate the previously reported association between elevated VIS and increased long-term mortality and assess if elevated VIS and other hemodynamic parameters increase the odds of right ventricular failure (RVF) within 30 days of LVAD implantation. Hypothesis Increased VIS following LVAD implantation will increase mortality and odds of developing RVF. Methods A single-center retrospective chart review was conducted for 235 patients with LVAD implantation and complete post-operative management from 2006-2016. The VIS was calculated as 100 x epinephrine + 100 x norepinephrine + 10 x milrinone + dopamine + dobutamine (μg/kg/min) + 1000 x vasopressin (U/kg/min) and was collected at 6, 24, and 48-hour intervals post-implantation. Patients were stratified by a maximum VIS score of 20 and compared via baseline demographics and comorbidities. Results The average maximum VIS for all patients was 15.38 (± 8.77). Those with a VIS ≥20 had a greater proportion of males (p = 0.046) and a history of obstructive sleep apnea (p = 0.002), MI (p = 0.005), CABG (p = 0.001), PCI (p = 0.007), and ICD placement (p = 0.003). (Table 1). Survival analysis found that VIS ≥ 20 was associated with increased 1-year mortality (HR 2.08, 95% CI [1.20- 3.31], p = 0.009) (Figure 1). In our multivariable logistic regression model a VIS ≥ 20 (OR 2.79, 95% CI [1.34- 5.79], p = 0.006) and a CVP/ PCWP >0.6 (OR 2.26, 95% CI [1.08- 4.73], p = 0.030) significantly increased the odds of early RVF. Conclusion Elevated VIS score in the first 48 hours following LVAD implantation is associated with an increased risk of mortality. Elevated VIS and CVP/PCWP >0.6 also increase the odds of early RVF. Further research with larger cohorts is needed to validate these findings as they could have significant implications on perioperative LVAD management.
Cytomegalovirus antiviral stewardship in the COVID-19 Era: Increasing complexity of prophylaxis and treatment and potential mitigation strategies.

Cytomegalovirus (CMV) infection is one of the most common and significant complications after solid organ transplant (SOT). Severe acute respiratory coronavirus 2 (SARS-CoV-2), which causes the novel betacoronavirus 2019 disease (COVID-19), has become the first global pandemic in 100 years. The world's attention has turned to address this unanticipated development; however, the viral infection that has long plagued outcomes after solid organ transplantation still requires vigilance. With physical distancing as the key intervention to reduce the healthcare burden, and the unease related to healthcare contact within the transplant population given the associated morbidity and mortality of COVID-19 in transplant recipients, providers have struggled to evaluate and streamline essential in-person healthcare contact, including laboratory visits. Owing to this, the COVID-19 pandemic has placed a significant strain on the delivery of CMV prophylaxis and treatment after solid organ transplantation. In this piece, we will describe issues our CMV antiviral stewardship service has encountered in the care of the transplant recipient with CMV during the this unprecedented time and share our expert opinion to approaches to providing optimal, evidenced based care during a pandemic associated with a seemingly unrelated viral infection.
Analysis of State-Level Immigrant Policies and Preterm Births by Race/Ethnicity Among Women Born in the US and Women Born Outside the US.

Importance Criminalizing immigrant policies, a form of structural racism, are associated with preterm birth; however, to date, few population studies have examined this association by race and nativity status or examined the association of inclusive immigrant policies with preterm birth. Objective To assess the extent to which variation in preterm birth by race/ethnicity and nativity status is associated with state-level criminalizing vs inclusive immigrant policies. Design, Setting, and Participants This retrospective, cross-sectional study analyzed birth record data from all 50 states and the District of Columbia in 2018, as well as state-level indicators of inclusive and criminalizing immigrant policies. White, Black, Asian, and Latina women who had singleton births were included in the study. Statistical analysis was performed from June 1, 2020, to February 5, 2021. Two continuous variables were created to capture the number of criminalizing vs inclusive immigrant policies in effect as of 2017 in each state. Main Outcomes and Measures The main outcome measure was preterm birth ( Results Among the 3 455 514 live births that occurred in 2018, 10.0% were preterm, and 23.2% were to mothers born outside the US. Overall, for women born outside the US, each additional state-level inclusive policy was associated with a 2% decrease in preterm birth (adjusted odds ratio [aOR], 0.98 [95% CI, 0.96-1.00]); there were no significant associations between inclusive policies and preterm birth among women born in the US. In models examining the combined associations of criminalizing and inclusive immigrant policies with preterm birth, each additional criminalizing policy was associated with a 5% increase in preterm birth among Black women born outside the US (aOR, 1.05 [95% CI, 1.00-1.10]). Each additional inclusive immigrant policy was associated with a lower likelihood of preterm birth for Asian women born in the US (aOR, 0.95 [95% CI, 0.93-0.98]) and White women born outside the US (aOR, 0.97 [95% CI, 0.95-0.99]). No significant associations were found among other groups. Conclusions and Relevance This study suggests that criminalizing immigrant policies are associated with an increase in preterm birth specifically for Black women born outside the US. Inclusive immigrant policies are associated with a decrease in preterm birth for immigrants overall, Asian women born in the US, and White women born outside the US. No associations were found between criminalizing or inclusive immigrant policies and preterm birth among Latina women.
InGaAsP/InP Membrane Gain Sections for III-V/SiN x Heterogeneous Photonic Integration

We present a fabrication process for 200 nm thick InGaAsP/InP membrane gain sections (λ = 1550 nm) suitable for heterogeneous integration with SiN x PICs. The structures exhibit desired electrical performance and support lasing.
Know Thy Enemies: The Competitive Sensemaking of Market

Due to an increasing dynamism in markets, changes in the competitive landscape have made the assessment of competitive boundaries an increasing concern to scholars of managements. The objective of this study is to develop a competitive sense-making approach to explain how firms develop a shared as well as ambiguous understanding of competitive boundaries. A unique contribution of this study is that it introduces an endogenous explanation of the competitive boundary process. This process appeals to a firm’s past (retrospective) and future (prospective) sense-making processes that not only define a firm’s competitive relationships, but these relationships create a shared and ambiguous understanding of competitive boundaries. A novel agent base simulation model was then developed to examine this competitive sense-making where it shows institutional influences involving population can moderate a firm’s competitive sense-making.
Data Action: Using Data for Public Good: Sarah Williams (2020). MIT Press, 312 pages, $39.95 (hardcover)

Let’s talk data. In the 2000s, a parade of books such as Strogatz’s Sync (2003), Watts’s Six Degrees (2004), Barabasi and Fragos’s Linked (2002) and Bursts (Barabasi, 2010), and Christakis and Fowl...
The SIMRAND methodology - Simulation of Research and Development Projects

In research and development projects, a commonly occurring management decision is concerned with the optimum allocation of resources to achieve the project goals. Because of resource constraints, management has to make a decision regarding the set of proposed systems or tasks which should be undertaken. SIMRAND (Simulation of Research and Development Projects) is a methodology which was developed for aiding management in this decision. Attention is given to a problem description, aspects of model formulation, the reduction phase of the model solution, the simulation phase, and the evaluation phase. The implementation of the considered approach is illustrated with the aid of an example which involves a simplified network of the type used to determine the price of silicon solar cells.
A Clarification and Extension of Multiple Use

Nearly every discipline, scientific or not, has one or more concepts that are perennially troublesome. Ecologists have argued for years about “competition”; philosophers have argued about “denotation” and “designation.” Forestry’s contribution is, without doubt, “multiple use.” But “multiple use” is different, for it is about power (Convery 1979). McArdle (1953) put it bluntly: “this is no penny ante game; the stakes are tremendous.” In a more philosophical vein, Hall (1963) quotes Charles A. Reich: “the power of the Forest Service is awesome, for the Service recognizes...that its job is nothing less than the definition of public good, a task once reserved for philosopher kings.” Because multiple use plays such an important role in forest management decision making, it bears further scrutiny.
Measurement of the Energy Content in Acousto-Ultrasonic Signals

Important features of the techniques currently employed for the measurement of acousto-ultrasonic (AU) parameter commonly referred to as stress wave factor are briefly described. An alternate procedure for characterizing this AU parameter, in which the energy content of the received signal is used to rank the material’s interaction with the propagating stress wave is proposed. This procedure employs simultaneous counting of acousto-ultrasonic signals at a number of threshold levels, suitably distributed across the amplitude range of the signals encountered in a particular test. The resulting counts at different threshold levels are given weightings according to their amplitudes and are summed up to provide a measure of energy. The accuracy of this scheme is verified by measuring the acoustical signals produced by the impact of steel spheres of different masses on a borosilicate glass block. In a related study, the same procedure was applied to measure acoustic emission signals from composite materials and was found to provide an estimate of the damage level with fair degree of success.
Hybrid PET/MRI as a tool to detect brown adipose tissue: Proof of principle

Summary Objective The purpose of this study was to assess the performance of 18 F-FDG hybrid PET/MRI to detect and localise the presence of metabolically active brown adipose tissue (BAT). Methods We retrospectively analyzed 197 consecutive 18 F-flurodeoxyglucose ( 18 F-FDG) positron-emission tomographic (PET) and magnetic resonance imaging (MRI) images performed with a hybrid whole-body PET–MRI tomography in 192 patients. These patients were originally investigated mainly for oncological staging, in the absence of a cooling protocol. The presence of BAT was defined as a soft tissue structure that was larger than 4mm in diameter, had the characteristics of fat tissue on MRI and had a maximal standardised uptake value (SUV) of 18 F-FDG of at least 2.0. No specific MRI sequences for BAT detection were acquired. Results PET/MRI identified the presence of metabolically active BAT in 5 out of 192 patients (2.6%). BAT positive subjects were all female, significantly younger and with significantly lower body weight than BAT negative subjects. Conclusions Whole body hybrid PET/MRI allowed for the identification of BAT, with a low prevalence, comparable to previous retrospective PET/CT studies realised in the absence of a cooling protocol. The main advantages of the PET/MRI hybrid technique, as compared with PET/CT, includes a lower radiation burden, and the possibility to combine a multiparameter fat characterization by dedicated MRI sequences. Hybrid PET/MRI might represent the ideal tool for BAT evaluation.
High power fast kicker system for SNS beam extraction

A Blumlein topology based high peak power, high repetition rate, and low beam impedance fast extraction kicker system for ORNL Spallation Neutron Source (SNS) is being developed at Brookhaven National Laboratory. The large magnet window size, large deflecting angle, low beam impedance termination and fast deflecting field rise time demand a very strong pulsed power source to drive the SNS extraction fast kicker magnet. This system consists of fourteen high voltage modulators and fourteen lumped kicker magnet sections. All modulators will be located in a service building outside the beam tunnel, which is a revised design requirement adopted in the mid 2000. The high current pulses generated by the high power modulators will be delivered through high voltage pulsed transmission cables to each kicker magnet sections. The designed output capacity of this system is in multiple GVA. Its first article modulator has been constructed and is being tested. In this paper, we present the system overview, project status and the advantages of this new conceptual design.
Tracking Bacterial Responses to Global Warming with an Ecotype-Based Systematics

The broadly defined species of bacterial systematics frequently contain unnamed and unrecognized populations (ecotypes) differing in physiology, genome content, and ecology. Without formal recognition of such ecotypes, it is difficult for microbial ecologists to detect replacement of one ecotype by another in the face of global warming. The ecotype simulation algorithm has proved capable of supporting investigation of such replacements, as it has detected temperature-distinguished ecotypes that are invisible to the present bacterial systematics. Creating an ecotype-based systematics will help to identify the units of diversity that we will want to track as we seek to observe the early microbial responses to global warming.
Pseudorabies virus infection of the rat central nervous system: ultrastructural characterization of viral replication, transport, and pathogenesis

Pseudorabies virus (PRV) has been used extensively to map synaptic circuits in the CNS and PNS. A fundamental assumption of these studies is that the virus replicates within synaptically linked populations of neurons and does not spread through the extracellular space or by cell- to-cell fusion. In the present analysis we have used electron microscopy to characterize pathways of viral replication and egress that lead to transneuronal infection of neurons, and to document the non-neuronal response to neuronal infection. Three strains of PRV that differ in virulence were used to infect preganglionic motor neurons in the dorsal motor nucleus of the vagus (DMV). The data demonstrate that viral replication and transneuronal passage occur in a stepwise fashion that utilizes existing cellular processes, and that the non-neuronal response to infection serves to restrict nonspecific spread of virus by isolating severely infected neurons. Specifically, capsids containing viral DNA replicate in the cell nucleus, traverse the endoplasmic reticulum to gain access to the cytoplasm, and acquire a bilaminar membrane envelope from the trans cisternae of the Golgi. The outer leaf of this envelope fuses with the neuron membrane to release virus adjacent to axon terminals that synapse upon the infected cell. A second fusion event involving the viral envelope and the afferent terminal releases the naked capsid into the bouton. Systematic analysis of serial sections demonstrated that release of virus from infected neurons occurs preferentially at sites of afferent contact. Nonspecific diffusion of virus from even the most severely infected cells is restricted by astrocytes and other non-neuronal elements that are mobilized to the site of viral infectivity. The ability of glia and macrophages to restrict spread of virus from necrotic neurons is the product of (1) temporal differences in the mobilization of these cells to the site of infection, (2) differential susceptibility of these cells to PRV infection, and (3) abortive viral replication in cells that are permissive for infection. The findings provide further insight into the intracellular routes of viral assembly and egress and support the contention that transneuronal spread of virus in the brain results from specific passage of virions through synaptically linked neurons rather than through cell fusion or release of virus into the extracellular space.
Automated translation of digital logic equations into VHDL code

A method for the automated translation of finite state machines from state table form to VHDL code is described. To do this, algorithms for reducing the state machine to simplest form, for making state assignments, for producing minimal logic equations to represent the state machine, and for producing VHDL code which describes the intended circuit are needed. Various algorithms were examined, and a prototype program was written to perform this translation. >
Rapid Detection of Clostridium botulinum Toxin by Capillary Tube Diffusion

A micro capillary agar-gel diffusion system for the detection of botulinal toxin in foods and cultures was developed and evaluated. Toxins types A, B, and E, produced in culture broth with and without added trypsin, and type E toxin, produced in inoculated canned clams, were tested with this system and with the mouse bioassay procedure. With nontrypsinized toxin, the capillary diffusion system detected as little as 100 minimal lethal doses (MLD) per ml but was effective only at higher levels, 10(6) to 1.5 x 10(7) MLD/ml, when used with trypsinized toxin. The inability to detect lower levels of trypsinized toxin was due to thioglycolate present in the medium used to produce toxin. Evidently, trypsinization of toxin produces polypeptides still held together by disulfide bonds. Cleavage of these bonds by reduction with thioglycolate reduces the sensitivity of the capillary method. Trypsinized toxin produced in broth without thioglycolate was detected as readily as nontrypsinized toxin. Toxin was detected in canned clams containing as low as 100 MLD/ml. No cross-reactions were observed with type E toxin and types A and B antitoxins. Extensive studies using the capillary method for detecting types A and B toxins were not performed; however, a suspected sample of commercially canned mushrooms gave a positive type B reaction but not a type A reaction. This typing was confirmed later by the mouse bioassay. Toxin was present at a level of 100 MLD/ml. The procedure developed may prove useful as a rapid screening method for the detection of botulinal toxin in foods, with final identification made by using the mouse bioassay.
Haematuria after prostate brachytherapy

What's known on the subject? and What does the study add? Previous descriptions of haematuria after brachytherapy are limited. This study characterizes the long-term incidence and associated clinical risk factors of haematuria after prostate brachytherapy. Objective To characterize the incidence and clinical history of gross haematuria after prostate brachytherapy. To identify treatment risk factors for the development of gross haematuria in this setting. Patients and Methods We reviewed haematuria outcomes collected prospectively in 2454 patients treated with transperineal prostate brachytherapy over a 20-year period at a single institution. Patients were followed for a median of 5.9 years. The association of haematuria with age, pretreatment PSA, ethnicity, clinical tumour stage, Gleason score, prostate volume, isotope (iodine 125 or palladium 103), biologically effective dose (BED), external beam radiation, androgen deprivation, development of urinary retention and occurrence of biochemical failure was investigated. Results A total of 218 men (8.9%) reported gross haematuria at a median time of 772.2 days after implantation. Haematuria was associated with prostate volume >40 cm3 (P 7 (P = 0.037), Asian ethnicity (P 200 Gy (P = 0.01), and freedom from biochemical failure (P = 0.004). On multivariate analysis, prostate volume >40 cm3 (P = 0.002), external beam radiation, (P = 0.001), and freedom from biochemical failure (P = 0.035) were predictors of haematuria. Conclusions Late gross haematuria was observed in a small proportion of men after brachytherapy and may occur with considerable latency. Larger prostate glands, freedom from biochemical failure and external beam radiation are risk factors.
Interference in the development of a secondary immune response in mice by zinc deprivation: persistence of effects

The purpose of this study was to determine the effects of a moderate period of zinc deficiency on the secondary responses of mice primed with antigen prior to nutritional insufficiency. Adult A/J mice were primed with sheep red blood cells (SRBC) 2 weeks prior to being placed on zinc-deficient, zinc-adequate or intake-restricted diets. After 28 days some of the mice in each treatment group were given a second injection of SRBC. Deficient mice could produce only 43% as many IgG anti-SRBC plaque-forming cells (PFC) per spleen as could the zinc-adequate or restricted-fed mice. To compare the secondary response of cells from each dietary group in a uniform environment, additional mice were killed as a source of primed splenocyte for transfer to irradiated hosts. Compared to controls, splenocytes from deficient mice gave suboptimal secondary responses even in normal irradiated hosts. Finally, the remaining mice were provided with zinc-adequate diet for a period of 4 weeks to allow for repair of the memory response, but it was only partially restored by this means. The data suggest that zinc deficiency may have destroyed a substantial portion of SRBC memory cells.
Biosynthesis of menaquinone (vitamin K2) and ubiquinone (coenzyme Q) : A perspective on enzymatic mechanisms

The benzoquinone ubiquinone (coenzyme Q) and the naphthoquinones menaquinone (vitamin K2) and demethylmenaquinone are derived from the shikimate pathway, which has been described as a "metabolic tree with many branches." Menaquinone (MK) is considered a vitamin, but coenzyme (Q) is not; MK is an essential nutrient (it cannot be synthesized by mammals), whereas Q is not considered an essential nutrient since it can be synthesized from the amino acid tyrosine. The quinone nucleus of Q is derived directly from chorismate, whereas that of MK is derived from chorismate via isochorismate. The prenyl side chain of both quinones is derived from prenyl diphosphate, and the methyl groups are derived from S-adenosylmethionine. MK biosynthesis requires 2-ketoglutarate and the cofactors ATP, coenzyme A (CoASH), and thiamine pyrophosphate. In spite of the fact that both quinones originate from the shikimate pathway, there are important differences in their biosynthesis. In MK biosynthesis, the prenyl side chain is introduced in the next to last step, which is accompanied by loss of the carboxyl group, whereas in Q biosynthesis, the prenyl side chain is introduced at the second step, with retention of the carboxyl group. In MK biosynthesis, all the reactions of the pathway up to the prenylation (next to last step) are carried out by soluble enzymes, whereas all the enzymes involved in Q biosynthesis except the first are membrane bound. In MK biosynthesis the last step is a C-methylation; in Q biosynthesis, the last step is an O-methylation. In Q biosynthesis a second C-methylation and O-methylation take place in the middle part of the pathway. In spite of the fact that Q and MK biosynthesis diverges at chorismate, the C-methylations involved in both pathways are carried out by the same enzyme. Finally, Q biosynthesis under aerobic conditions requires molecular oxygen; anaerobic biosynthesis of Q and MK incorporates oxygen atoms derived from water. The current status of the pathways with particular emphasis on the reaction mechanisms, is discussed in this review.
The Role of the United States Federal Food and Drug Administration: Regulator, Watchdog, Facilitator or All of These?

What would transpire if the United States Federal Food and Drug Administration (FDA) did not exist? The mission of the FDA is the promotion of the public health through prompt and efficient review of clinical research, and the taking of appropriate action on the marketing of regulated products in a timely manner. But, is the FDA a regulating agency? Is the FDA a watchdog agency? Or is the FDA a facilitating agency? The simplest and most obvious answer is that the FDA functions as all three. The relationship between the multi-functional role of the FDA and how to ensure that drug companies will comply with the agency provides the basis for this article.Drug manufacturers have motivation to produce safe and efficacious products – market reputation and profit. In other words, it is in the best interest of drug manufacturers to self-regulate because without safe and effective products, drug firms would self-destruct. So why does the FDA find it necessary to implement stringent approval processes and postmarket drug surveillance? History strongly suggests that although most companies would undertake appropriate precautions to ensure public safety, quackery and negligence can never be fully eradicated, thus justifying regulation and a strong regulatory body to promulgate laws.The expanse of FDA regulation is all-encompassing. That is, FDA regulatory authority extends to numerous products such as foods, human and veterinary drugs, medical devices, cosmetics, dietary supplements, biologics, and tobacco. However, this article will focus on pharmaceutical regulation to explore the interplay between FDA and the regulated industry. First, an historical overview will provide the origin for the need, foundation, and development of regulation geared towards drug law regulation as it exists in the United States today. Second, the FDA will be analyzed based on its functions as regulator, watchdog, and facilitator. Each of the three sections will address the ultimate question posed of how the FDA can ensure that drug companies will comply with regulations, and further draw conclusions as to whether the pharmaceutical industry could, or would, self-regulate so as to comply with Congressional mandates in the absence of the FDA.A look back at history, case law, and the expansive reach of the FDA strongly suggests that while many, if not most drug companies, would comply or attempt to comply with federal law to ensure public health, a climate without a strong administrative agency to oversee the pharmaceutical industry cannot be justified.
The Spatial Resolution of Rayleigh Wave, Acoustoelastic Measurement of Stress

One of the challenges in the acoustoelastic measurement of stress is the achievement of high spatial resolution. Since stress induced velocity shifts are generally small (~0.01%), the required precision of time and distance measurements can be quite high for the short propagation distances required. This paper presents a set of design criteria which can guide the experimentalist in choosing the most suitable measurement configuration for Rayleigh wave techniques. Three approaches for measuring the acoustic velocity are considered: measurement of arrival time versus transducer separation for several discrete positions, measurement of arrival time for a pair of transducers at a fixed separation, and inference of the velocity from the V(z) response of an acoustic microscope. For each case, analytical formulae are developed which relate the precision of velocity measurement to the experimental parameters and the expected uncertainty in the data. These formulae are confirmed by comparison to experiment.
Protein Composition of the Cell Wall and Cytoplasmic Membrane of Escherichia coli

Envelope preparations obtained by passing Escherichia coli cells through a French pressure cell were separated by sucrose density gradient centrifugation into two distinct particulate fractions. The fraction with the higher density was enriched in fragments derived from the cell wall, as indicated by the high content of lipopolysaccharide, the low content of cytochromes, and the similar morphology of the fragments and intact cell walls. The less-dense fraction was enriched in vesicles derived from the cytoplasmic membrane, as indicated by the enrichment of cytochromes, the enzymes lactic and succinic dehydrogenase and nitrate reductase, and the morphological similarity of the vesicles to intact cytoplasmic membrane. Both fractions were rich in phospholipid. The protein composition was compared by mixing the cytoplasmic membrane-enriched fraction from a (3)H-labeled culture with the cell wall-enriched fraction from a (14)C-labeled culture and examining the resulting mixture by gel electrophoresis. Thirty-four bands of radioactive protein were resolved; of these, 27 were increased two- to fourfold in the cytoplasmic membrane-enriched fraction, whereas 6 were similarly increased in the cell wall-enriched fraction. One of the proteins which is clearly localized in the cell wall is the protein with a molecular weight of 44,000, which is the major component of the envelope. This protein accounted for 70% of the total protein of the cell wall, and its occurrence in the envelope from spheroplasts suggests that it is a structural protein of the outer membranous component of the cell wall.
Predicting solution aggregation rates for therapeutic proteins: approaches and challenges.

Abstract Non-native aggregation is a common concern during therapeutic protein product development and manufacturing, particularly for liquid dosage forms. Because aggregates are often net irreversible under the conditions that they form, controlling aggregate levels requires control of aggregation rates across a range of solution conditions. Rational design of product formulation(s) would therefore benefit greatly from methods to accurately predict aggregation rates. This article focuses on the principles underlying current rate-prediction approaches for non-native aggregation, the limitations and strengths of different approaches, and illustrative examples from the authors’ laboratories. The analysis highlights a number of reasons why accurate prediction of aggregation rates remains an outstanding challenge, and suggests some of the important areas for research to ultimately enable improved predictive capabilities in the future.
Chalcogenide glass fiber-based MID-IR sources and applications

Naval Research Laboratory (NRL) is developing chalcogenide glass fibers for applications in the mid and long wave IR wavelength regions from 2-12 mm. The chalcogen glasses (i.e., glasses based on the elements S, Se, and Te) are transparent in the IR, possess low phonon energies, are chemically durable and can be drawn into fiber. Both conventional solid core/clad and microstructured fibers have been developed. Chalcogenide glass compositions have been developed which allow rare earth doping to enable rare earth doped fiber lasers in the IR. Also, highly nonlinear compositions have also been developed with nonlinearities ~1000x silica which enables nonlinear wavelength conversion from the near IR to the mid and long wave IR. In this paper, we review rare earth doped chalcogenide fiber for mid and long wave IR lasers and highly nonlinear chalcogenide fiber and photonic crystal fiber for wavelength conversion in the mid and long wave IR.
Population increase and family planning in Guatemala.

Guatemala which has an unusually high annual growth rate of 3.1% (1950-1964) is composed of Ladinos (53%) and Maya (47%). Previous KPA studies conducted among the Ladino population have indicated that 34.5% of the sample actually use contraceptives while 76.5% desire to receive information on birth control methods. In 1 KAP study (1966) conducted among Maya 85-88% had not heard about contraception while 39% of the men and 49% of the women were willing to accept contraceptive information. 96% of the men and 100% of the women in 1 study had never used contraceptives. It is important that more paraprofessionals who are indigenous to the target culture be recruited as family planning personnel. Maya community development and health projects are also needed. Health departments which serve urban areas in which Maya are located could also probably achieve quick family planning results as more Indians are literate in these areas and literacy has a strong positive correlation with acceptance of birth control.
Estimating the Correlation in Bivariate Normal Data with Known Variances and Small Sample Sizes

We consider the problem of estimating the correlation in bivariate normal data when the means and variances are assumed known, with emphasis on the small sample case. We consider eight different estimators, several of them considered here for the first time in the literature. In a simulation study, we found that Bayesian estimators using the uniform and arc-sine priors outperformed several empirical and exact or approximate maximum likelihood estimators in small samples. The arc-sine prior did better for large values of the correlation. For testing whether the correlation is zero, we found that Bayesian hypothesis tests outperformed significance tests based on the empirical and exact or approximate maximum likelihood estimators considered in small samples, but that all tests performed similarly for sample size 50. These results lead us to suggest using the posterior mean with the arc-sine prior to estimate the correlation in small samples when the variances are assumed known.
Ray analysis of mutual coupling between antennas on a convex surface

An approximate asymptotic solution is presented for the electromagnetic fields which are induced on an electrically large perfectly conducting smooth convex surface by an infinitesimal magnetic or electric current moment on the same surface. This solution can be employed to calculate the mutual coupling between antennas on a convex surface in an efficient and accurate manner. In this solution, the surface fields propagate along Keller's surface ray paths, and their description remains uniformly valid within the shadow boundary transition region including the immediate vicinity of the source. Furthermore, the effect of surface ray torsion on the surface fields is indicated in the present solution, through a factor T/k , where T denotes the surface ray torsion and k is the surface curvature in the ray direction. This solution is deduced from the asymptotic solutions to simpler canonical problems. Numerical results for the mutual coupling between slots in cylinders and cones are presented, and are shown to compare very well with experiments.
Evolution and gradualness

Evolutionary systems are commonly considered to have fundamental properties: (1) elements (or organisms) in the system reproduce with mutation and (2) only the fit elements survive. I propose that evolutionary systems have a third property - the property of gradualness. A system has gradualness, if, and only if, small changes in an element usually lead to small changes in that element's fitness. I have formalized a framework from which attempts to design evolutionary systems might proceed. Of particular importance are the criteria, based on the notion of perpetuation, which a system's behavior must satisfy in order to be considered evolutionary. By my standards, no computer programs have been designed that manifest meaningful evolutionary behavior.
Modulation of MEK activity during G-CSF signaling alters proliferative versus differentiative balancing

Previous studies of the granulocyte colony stimulating factor (G-CSF) receptor have demonstrated that discrete signals direct proliferative and maturation signaling. Receptor deletion/mutant studies have shown that although activation of the ras-mitogen activated protein (MAP) kinase pathway is necessary for G-CSF directed proliferation, it is not necessary for maturation induced by this cytokine. We have assessed the effects of selective inhibition or overexpression of MAP kinase kinase (MEK) in a cell line model of G-CSF-induced neutrophil progenitor growth. Using the human G-CSF responsive MPD cell line, we specifically inhibited MEK using PD 98059 and also transfected MPD cells with a constitutively active MEK construct. We then exposed the cells to G-CSF and assessed the effects of MEK inhibition and forced expression on proliferation and differentiation. Inhibition of MEK followed by G-CSF stimulation consistently resulted in an early 2.5-fold increase in morphologically differentiated neutrophils expressing CD11b and CD16 and containing lactoferrin over that produced by G-CSF alone. MEK inhibition alone had little effect on the differentiation stage of these cells, although proliferation was impaired. Forced expression of activated MEK resulted in a three- to five-fold decrease in differentiated, lactoferrin containing neutrophilic cells resultant from G-CSF induction, and a commensurate increase in cell proliferation. These observations suggest that modulation of MAPK activation may be a control point for altering the balance between proliferation and differentiation in response to G-CSF. Physiologically, this control is likely exerted by costimulatory cytokines.
Mapping the determinants of human immunodeficiency virus 2 for infectivity, replication efficiency, and cytopathicity.

Abstract Human immunodeficiency virus 2 (HIV-2) ISY and the newly derived HIV-2KR are infectious molecular clones that yield viruses differing markedly in their abilities to infect and/or induce syncytia in various T- and monocytoid-cell lines. Chimeric viruses were constructed from these two viral genomes to localize the genetic determinants of some of these properties. Envelope sequences, particularly those spanning the CD4 binding site, appear to be critical for the ability of HIV-2KR to infect MOLT-4 clone 8 and SupT1 cells and to efficiently infect the H9 cell line. On the other hand, multiple determinants may contribute to cytopathicity (gp41 and nef) in H9 cells and replication efficiency in monocytic (THP-1) cells.
Office Removal of a Subglottic Bread Clip

Objective. The presence of an upper airway foreign body is an emergent, potentially life-threatening situation that requires careful but rapid evaluation and management. Organic or nonorganic material may typically be found in the pyriform sinuses or tongue base or may be aspirated directly into the tracheobronchial tree. We present here an unusual case report of a patient who accidentally ingested a plastic bread clip that was lodged in his subglottis for 15 months and report successful removal in the office under local anesthesia. Methods. Mucosal anesthesia was achieved with inhaled 4% lidocaine spray. Flexible laryngoscopic removal of the foreign body was then successfully accomplished. Results. The patient's symptoms resolved completely following removal, with no sequelae. Conclusions. Office removal of airway foreign bodies is feasible and can be safely done with adequate topical anesthesia, but great caution and emergency planning must be exercised.
The Value Relevance of Earnings and Nonearnings Information in Regulated and Deregulated Markets: The Case of the Airline Industry

This paper examines the valuation effects of earnings and two nonearnings-based measurements (book values and operating cash flow) on security prices of airline companies under two different market structures: regulated and deregulated. The literature lacks empirical evidence in examining the relative importance of earnings and nonearnings accounting-based measurements in regulated and deregulated markets, especially in the airlines industry. We compare coefficient estimates of regressing stock prices on earnings, book value, and cash flow from operations of airline companies during regulated and deregulated times. A control sample of manufacturing companies is also used for supporting inferences from the airline sample’s findings. In a typical regulated market, using cost recovery plus an adequate rate of return on assets, security prices are highly aligned with nonearnings measurements such as the book value. In the airline industry, regulation took the form of guaranteed routes and subsidies to service rural areas, giving rise to a differential effect of both earnings and nonearnings measurements. Under deregulation, airline firms operate in highly competitive markets with large airline firms enjoying the benefits of economy of scale and service diversification. Thus, the asset capitalization (book value), cash flow, and operational efficiencies (earnings) would be major indicators in the market assessment of the firm’s future profitability and security price. This paper finds that nonearnings measures have higher explanatory power of security prices in regulated times for the airline firms. In deregulated times, although earnings have a stronger relationship with prices, nonearnings measures continued to influence stock price levels, reflecting airline specific economics.
α-Adrenergic Inhibition of Adenosine 3′,5′-Monophosphate Accumulation and Parathyroid Hormone Release from Dispersed Bovine Parathyroid Cells

The possibility of alpha-adrenergic modulation of cAMP accumulation and parathyroid hormone (PTH) release was investigated in dispersed bovine parathyroid cells. cAMP accumulation due to the mixed alpha- and beta-adrenergic agonists, (-)epinephrine and (-)norepinephrine, was significantly enhanced by the alpha-adrenergic inhibitor phentolamine; that due to the "pure" beta-adrenergic agonist, (-)isoproterenol, was not altered significantly. Direct inhibition of agonist-stimulated cAMP accumulation was effected by adding increasing concentrations of (-)epinephrine to concentrations of (-)isoproterenol maximally stimulating cAMP accumulation. A 50-75% inhibition of cAMP was observed which was specifically blocked by phentolamine. This inhibition was not specific for beta-adrenergic stimulation, as (-)epinephrine also inhibited dopamine-stimulated cAMP accumulation. The inhibition of (-)isoproterenol-stimulated cAMP accumulation by (-)epinephrine was unaffected by ambient calcium concentration. Stimulation of PTH release by (-)epinephrine and (-)norepinephrine was potentiated by phentolamine and inhibited by the beta-adrenergic blocker, (-)propranolol, demonstrating alpha-adrenergic modulation of hormone release and confirming the close relationship between cAMP accumulation and PTH release previously shown in this system. These results demonstrate the presence of an alpha-adrenergic receptor in dispersed bovine parathyroid cells which inhibits agonist-stimulated cAMP accumulation and PTH release by a mechanism independent of extracellular calcium.
Preparative Centrifugal Precipitation Chromatography Using Dialysis Membrane Inserted into Convoluted Tubing

Abstract The method uses preparative centrifugal precipitation chromatography comprising a seal‐free continuous‐flow centrifuge machine equipped with a plastic disk and a spiral groove which accommodates convoluted tubing. A dialysis membrane is inserted into the convoluted tubing to separate proteins according to their solubility in ammonium sulfate solution. The system relies on the original model of centrifugal precipitation chromatography, which employs the centrifugal force and a concentration gradient of precipitants to perform a repetitive process of precipitation and dissolution of protein molecules. Compared to the previous model, the current model results in a higher yield of separated compounds.
Fostering Children's Interests in Gardening.

Despite the rapidly growing interest in children's gardens and attention to the positive benefits of gardening for children, little is known about the ways in which young people actually form inter...
The efficient, scale-invariant determination of starting step sizes for high-order integrators

Many routines for solving differential equations require the user to specify an estimate of the initial step size. We introduce a means of estimating an appropriate value automatically. Strong emphasis is placed on the need for scale invariance in making such estimates, and we therefore review the importance of scale and matters equivalent to scale in estimating the order of magnitude of the appropriate starting step size. In this context, we also discuss the response to scale of integrators employing the error per unit step concept of error control and are forced to conclude that our procedure should not be used in such integrators, if the latter should be used at all. We note a special case where the procedure could be badly deceived and suggest an option by which the user can protect himself against this kind of mishap. Test results are cited.
Application of soil surveys to selection of sites for on-site disposal of liquid household wastes

Safe disposal of liquid household wastes in unsewered areas is often accomplished by using a septic tank followed by subsurface soil disposal of effluent in a seepage bed. Many soils are unsuitable for this type of on-site disposal because of low permeability, close proximity to high groundwater or shallow bedrock. Soil maps are a useful tool for delineating potential problem areas and thus have come into use for purposes of selecting and evaluating building sites and for local and regional land use planning. Soil survey methodology is a useful complement to conventional site evaluation techniques. Innovative technology for on-site liquid waste disposal may be applicable for many sites that are unsuitable for traditional systems. Soil surveys are then quite useful to indicate the extent of areas in which the new technology may be applied. However, incorporation of soil information into such innovative systems will usually require a more detailed in-situ characterization of hydraulic characteristics than is currently provided by soil surveys. Successful implementation of the new technology and new uses for soil information requires cooperative interdisciplinary efforts among local, state and national health officials, soil scientists, governmental officials who develop and enforce laws and regulations, extension educators, engineers, research scientists, plumbers and home-owners. Such integrated efforts can bring about significant changes in the on-site disposal of liquid household wastes.
Preparations of polymers using metal-carbenes

Abstract Metal-carbenes initiate the polymerizations of cycloalkenes to polyalkenamers that are stereoselectively cis, cyclic trisubstituted olefins to polymers that are translationally invariant, and acetylenes to polyacetylenes. Some implications are described.