cssi/SciSciGPT-SciSciNet huggingface dataset:
Postnatal changes of plasma amino acids in suckling pigs.

Amino acids, ammonia, urea, orotate, and nitrate plus nitrite (stable oxidation products of nitric oxide) were determined in plasma of 1- to 21-d-old suckling pigs. Jugular venous blood samples were obtained from pigs at 1, 3, 7, 14, and 21 d of age for analysis of plasma amino acids and metabolites by HPLC and enzymatic methods. Plasma concentrations of arginine and its immediate precursors (citrulline and ornithine) decreased (P 0.05) in plasma concentrations of other amino acids. Plasma concentrations of ammonia increased (P < 0.01) by 18 and 46%, whereas those of nitrate plus nitrite decreased (P < 0.01) by 16 and 29%, in 7- and 14-d-old pigs, respectively, compared with 1- to 3-d-old pigs. Because arginine plays a crucial role in ammonia detoxification via the hepatic urea cycle and is the physiological substrate for nitric oxide synthesis, our results of the decreased plasma concentrations of arginine and nitrate plus nitrite, as well as the increased plasma ammonia concentration, indicate a hitherto unrecognized deficiency of arginine in 7- to 21-d-old suckling pigs. Arginine is an essential amino acid for piglets and has a great potential to enhance neonatal growth; therefore, further studies are necessary to elucidate the mechanism responsible for arginine deficiency in sow-reared piglets and to identify hormonal and metabolic means for improving neonatal arginine nutrition and growth.
The Integrated Model Evaluation System (IMES): A Database for Evaluation of Exposure Assessment Models

The USEPA Office of Health and Environmental Assessment develops methodologies for conducting exposure and risk assessments. Protocols appropriate for specific analyses have been developed to aid in the selection of an exposure assessment model and to assess the validation and uncertainties associated with models used for toxic chemical exposure assessments in surface water, groundwater, and air. A software package has been developed to provide users with a quick and intuitive tool to access information for selected models and applications based on these protocols. The Integrated Model Evaluation System (IMES) is composed of three modules: 1) Selection, query systems for selecting a model based on technical criteria (currently for surface water, non-point source, and groundwater models); 2) Validation, a database containing validation and other information on over 50 models in various media; and 3) Uncertainty, a database demonstrating uncertainty simulations for several surface water models applied to exposure assessments of several chemicals. The selection modules are linked to the uncertainty and validation modules to access information for chosen models. The PC-based software system employs pull-down menus, help screens, and graphics to display its information.
Allosteric Drug Effects

Abstract This chapter begins with a discussion of the characteristic properties of an allosteric molecule, namely saturability of effect (the allosteric modulation ends when the allosteric site is fully occupied), probe dependence (the allosteric effect of a given modulator can be different for different cobinding ligands) and the production of separate effects on the affinity and efficacy of the cobinding ligand. In addition, the strategies for identifying allosterism and the reasons why this is relevant to drug discovery are featured. Specifically, these involve the unique therapeutic properties of allosteric modulators. Finally, the use of pharmacologic tools to quantify allosteric behavior of molecules in studies aimed at optimization of allosteric activity will be highlighted. Once allosterism has been identified as a mechanism, then comparison of data to an allosteric model can be used to identify characteristic parameters of the effect.
The role of glucocorticoids in the vertebrate response to weather

Abstract Changes in the environment related to inclement weather can threaten survival and reproductive success both through direct adverse exposure and indirectly by decreasing food availability. Glucocorticoids, released during activation of the hypothalamic-pituitary-adrenal axis as part of the stress response, are an important candidate for linking vertebrate coping mechanisms to weather. This review attempts to determine if there is a consensus response of glucocorticoids to exposure to weather-related stimuli, including food availability, precipitation, temperature and barometric pressure. The included studies cover field and laboratory studies for all vertebrate taxa, and are separated into four exposure periods, e.g., hours, days, weeks and months. Each reported result was assigned a score based on the glucocorticoid response, e.g., increased, no change, or decreased. Short-term exposure to weather-related stimuli, of up to 24 h, is generally associated with increased glucocorticoids (79% of studies), suggesting that these stimuli are perceived as stressors by most animals. In contrast, the pattern for exposures longer than 24 h shows more variation, even though a majority of studies still report an increase (64%). Lack of glucocorticoid increases appeared to result from instances where: (1) prolonged exposure was a predictable part of the life history of an animal; (2) environmental context was important for the ultimate effect of a stimulus (e.g., precipitation limited food availability in one environment, but increased food in another); (3) prolonged exposure induced chronic stress; and (4) long-term responses appeared to reflect adaptations to seasonal shifts, instead of to short-term weather. However, there is a strong bias towards studies in domesticated laboratory species and wild animals held in captivity, indicating a need for field studies, especially in reptiles and amphibians. In conclusion, the accumulated literature supports the hypothesis that glucocorticoids can serve as the physiological mechanism promoting fitness during inclement weather.
Predicting image properties in penalized-likelihood reconstructions of flat-panel CBCT

Purpose Model-based iterative reconstruction (MBIR) algorithms such as penalized-likelihood (PL) methods exhibit data-dependent and shift-variant properties. Image quality predictors have been derived to prospectively estimate local noise and spatial resolution, facilitating both system hardware design and tuning of reconstruction methods. However, current MBIR image quality predictors rely on idealized system models, ignoring physical blurring effects and noise correlations found in real systems. In this work, we develop and validate a new set of predictors using a physical system model specific to flat-panel cone-beam CT (FP-CBCT). Methods Physical models appropriate for integration with MBIR analysis are developed and parameterized to represent nonidealities in FP projection data including focal spot blur, scintillator blur, detector aperture effect, and noise correlations. Flat-panel-specific predictors for local spatial resolution and local noise properties in PL reconstructions are developed based on these realistic physical models. Estimation accuracy of conventional (idealized) and FP-specific predictors is investigated and validated against experimental CBCT measurements using specialized phantoms. Results Validation studies show that flat-panel-specific predictors can accurately estimate the local spatial resolution and noise properties, while conventional predictors show significant deviations in the magnitude and scale of the spatial resolution and local noise. The proposed predictors show accurate estimations over a range of imaging conditions including varying x-ray technique and regularization strength. The conventional spatial resolution prediction is sharper than ground truth. Using conventional spatial resolution predictor, the full width at half maximum (FWHM) of local point spread function (PSF) is underestimated by 0.2 mm. This mismatch is mostly eliminated in FP-specific prediction. The general shape and amplitude of local noise power spectrum (NPS) FP-specific predictions are consistent with measurement, while the conventional predictions underestimated the noise level by 70%. Conclusion The proposed image quality predictors permit accurate estimation of local spatial resolution and noise properties for PL reconstruction, accounting for dependencies on the system geometry, x-ray technique, and patient-specific anatomy in real FP-CBCT. Such tools enable prospective analysis of image quality for a range of goals including novel system and acquisition design, adaptive and task-driven imaging, and tuning of MBIR for robust and reliable behavior.
Role-Based Faultlines and Intragroup Conflict

I explore the possibility of group roles and role behaviors acting as group faultlines. Utilizing the three broad role categories proposed by Mumford, Campion, & Morgeson (2006), I develop a model ...
Patterns of Implicit and Explicit Attitudes: I. Long-Term Change and Stability From 2007 to 2016:

Using 4.4 million tests of implicit and explicit attitudes measured continuously from an Internet population of U.S. respondents over 13 years, we conducted the first comparative analysis using time-series models to examine patterns of long-term change in six social-group attitudes: sexual orientation, race, skin tone, age, disability, and body weight. Even within just a decade, all explicit responses showed change toward attitude neutrality. Parallel implicit responses also showed change toward neutrality for sexual orientation, race, and skin-tone attitudes but revealed stability over time for age and disability attitudes and change away from neutrality for body-weight attitudes. These data provide previously unavailable evidence for long-term implicit attitude change and stability across multiple social groups; the data can be used to generate and test theoretical predictions as well as construct forecasts of future attitudes.
Change in Survival in Metastatic Breast Cancer with Treatment Advances: Meta-Analysis and Systematic Review

Background Metastatic breast cancer (MBC) treatment has changed substantially over time, but we do not know whether survival post-metastasis has improved at the population level. Methods We searched for studies of MBC patients that reported survival after metastasis in at least two time periods between 1970 and the present. We used meta-regression models to test for survival improvement over time in four disease groups: recurrent, recurrent estrogen (ER)-positive, recurrent ER-negative, and de novo stage IV. We performed sensitivity analyses based on bias in some studies that could lead earlier cohorts to include more aggressive cancers. Results There were 15 studies of recurrent MBC (N = 18 678 patients; 3073 ER-positive and 1239 ER-negative); meta-regression showed no survival improvement among patients recurring between 1980 and 1990, but median survival increased from 21 (95% confidence interval [CI] = 18 to 25) months to 38 (95% CI = 31 to 47) months from 1990 to 2010. For ER-positive MBC patients, median survival increased during 1990-2010 from 32 (95% CI = 23 to 43) to 57 (95% CI = 37 to 87) months, and for ER-negative MBC patients from 14 (95% CI = 11 to 19) to 33 (95% CI = 21 to 51) months. Among eight studies (N = 35 831) of de novo stage IV MBC, median survival increased during 1990-2010 from 20 (95% CI = 16 to 24) to 31 (95% CI = 24 to 39) months. Results did not change in sensitivity analyses. Conclusion By bridging studies over time, we demonstrated improvements in survival for recurrent and de novo stage IV MBC overall and across ER-defined subtypes since 1990. These results can inform patient-doctor discussions about MBC prognosis and therapy.
Teaching Video NeuroImages: MT-TL1 mutation presenting as chronic progressive external ophthalmoplegia.

A 19-year-old woman presented with bilateral ptosis and progressive ophthalmoparesis with onset at least 7 years prior. Family history was pertinent for a great aunt with bilateral ptosis. Neurologic examination was positive for bilateral ptosis with near complete ophthalmoplegia (video), otherwise unremarkable. Retinal examination showed no pigmentary changes. Cardiac evaluation and EMG were normal. Orbicularis oculi biopsy confirmed mitochondrial hyperplasia and ragged-red fibers. Blood testing was positive for a pathogenic variant in MT-TL1 (m.3243A>G), most commonly associated with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes.1 Chronic progressive external ophthalmoplegia is a rare though not novel presentation of this mutation.2
Increased streamflow in catchments affected by a forest disease epidemic

Natural disturbances help maintain healthy forested and aquatic ecosystems. However, biotic and abiotic disturbance regimes are changing rapidly. For example, the Swiss needle cast (SNC) epidemic in the Coast Range of Oregon in the U.S. Pacific Northwest has increased in area from 53,050 to 238,705ha over the 1996-2015 period. We investigated whether the hydrologic regime (i.e., annual streamflow, runoff ratio, and magnitude and timing of peak flows and low flows) was affected by SNC in 12 catchments in western Oregon. The catchments ranged in size from 183 to 1834km2 and area affected by SNC from 0 to 90.5%. To maximize the number of catchments included in the study, we analyzed 20years of SNC aerial survey data and 15-26years of stream discharge (Q) and PRISM precipitation (P) and air temperature (Tair) data to test for trends in hydrologic variables for each catchment. As expected, we found that runoff ratios (Q/P) increased in five catchments, all with an area impacted by SNC >10%. This was likely due to the effects of SNC on the hydraulic architecture (i.e., needle retention, sapwood area, sapwood permeability) of affected trees, leading to decreased canopy interception and transpiration losses. Interestingly, two catchments with the greatest area affected by SNC showed no changes in hydrologic regime. The lack of hydrologic response could either be due to compensatory transpiration by vegetation unaffected by the disease or sub-canopy abiotic evaporation, which counteracted reductions in transpiration. This study is the first to illustrate that chronic canopy disturbance from a foliage pathogen can influence catchment scale hydrology.
Pasteurella multocida vertebral osteomyelitis, myositis and epidural abscess in a diabetic cirrhotic patient

Abstract Pasteurella multocida is frequently associated with soft tissue infections related to animal bites or scratches. These infections are usually mild but can lead to serious complications especially in high-risk patients. We present a chronic Pasteurella. multocida vertebral osteomyelitis with extensive spondylodiscitis, myositis and epidural abscess in a patient with diabetes and liver cirrhosis. Pasteurella multocida should be suspected in bone and soft tissue infections even if the site of infection is distant to the site of the animal bite, scratch or lick, especially in high-risk patients.
Fluids, Salts and Blood

Publisher Summary This chapter discusses the management of fluid losses occurring during injuries. Intravascular volume is a major consideration in multiple system trauma. At present, most of the concepts of fluid resuscitation are based upon the work of Shirers and his colleagues. Their work using dogs as a hemorrhagic shock model demonstrated that resuscitation carried out with only blood, or blood in conjunction with colloid-containing solutions, was associated with a high mortality approximating 70%. Only with the addition of balanced electrolyte-containing solutions, such as Ringer's lactate solution, was mortality reduced to about 20%–30%. Volume loss is recognized as a major defect during shock. Hypovolemia induces interstitial fluid movements into the intravascular compartment at the expense of interstitial volume. This form of autotransfusion is the body's attempt to maintain normal circulating volume. The chapter discusses fluid losses that occur during hemorrhagic shock. It describes the appropriate types of fluid to be used during resuscitation and the pros and cons of each. The chapter also discusses the differences between balanced electrolyte and albumin-containing solutions.
Understanding the seasonal variations of Peninsular Florida

This study accounts for varying lengths of the seasons, which turns out to be an important consideration of climate variability over Peninsular Florida (PF). We introduce an objective definition for the onset and demise of the winter season over relatively homogenous regions within PF: North Florida (NF), Central Florida (CF), Southeast Florida (SeF), and Southwest Florida (SwF). We first define the summer season based on precipitation, and follow this by defining the winter season using surface temperature analysis. As a consequence, of these definitions of the summer and the winter seasons, the lengths of the transition seasons of spring and fall also vary from year to year. The onset date variations have a robust relationship with the corresponding seasonal length anomalies across PF for all seasons. Furthermore, with some exceptions, the onset date variations are associated with corresponding seasonal rainfall and surface temperature anomalies, which makes monitoring the onset date of the seasons a potentially useful predictor of the following evolution of the season. In many of these instances the demise date variations of the season also have a bearing on the preceding seasonal length and seasonal rainfall anomalies. However, we find that variations of the onset and the demise dates are independent of each other across PF and in all seasons. We also find that the iconic ENSO teleconnection over PF is exclusive to the seasonal rainfall anomalies and it does not affect the variations in the length of the winter season. Given these findings, we strongly suggest monitoring and predicting the variations in the lengths of the seasons over PF as it is not only an important metric of climate variability but also beneficial to reduce a variety of risks of impact of anomalous seasonal climate variations.
A Narrative Study of Equity in Clinical Assessment Through the Antideficit Lens.

Purpose Efforts to address inequities in medical education are centered on a dialogue of deficits that highlight negative underrepresented in medicine (UIM) learner experiences and lower performance outcomes. An alternative narrative explores perspectives on achievement and equity in assessment. This study sought to understand UIM learner perceptions of successes and equitable assessment practices. Method Using narrative research, investigators selected a purposeful sample of self-identified UIM fourth-year medical students and senior-level residents and conducted semi-structured interviews. Questions elicited personal stories of achievement during clinical training, clinical assessment practices that captured achievement, and equity in clinical assessment. Using re-storying and thematic analysis, investigators coded transcripts and synthesized data into themes and representative stories. Results Twenty UIM learners (6 medical students and 14 residents) were interviewed. Learners often thought about equity during clinical training and provided personal definitions of equity in assessment. Learners shared stories that reflected their achievements in patient care, favorable assessment outcomes, and growth throughout clinical training. Sound assessments that captured achievements included frequent observations with real-time feedback on pre-defined expectations by supportive, longitudinal clinical supervisors. Finally, equitable assessment systems were characterized as sound assessment systems that also avoided comparison to peers, used narrative assessment, assessed patient care and growth, trained supervisors to avoid bias, and acknowledged learner identity. Conclusions UIM learners characterized equitable and sound assessment systems that captured achievements during clinical training. These findings guide future efforts to create an inclusive, fair, and equitable clinical assessment experience.
Perioperative morbidity and mortality of patients with COVID-19 who undergo urgent and emergent surgical procedures

Objective To evaluate the perioperative morbidity and mortality of patients with COVID-19 who undergo urgent and emergent surgery. Summary background data Although COVID-19 infection is usually associated with mild disease, it can lead to severe respiratory complications. Little is known about the perioperative outcomes of patients with COVID-19. Methods We examined patients who underwent urgent and emergent surgery at 2 hospitals in New York City from March 17 to April 15, 2020. Elective surgical procedures were cancelled throughout and routine, laboratory based COVID-19 screening was instituted on April 1. Mortality, complications, and admission to the intensive care unit were compared between patients with COVID-19 detected perioperatively and controls. Results Among 468 subjects, 36 (7.7%) had confirmed COVID-19. Among those with COVID-19, 55.6% were detected preoperatively and 44.4% postoperatively. Before the routine preoperative COVID-19 laboratory screening, 7.7% of cases were diagnosed preoperatively compared to 65.2% after institution of screening (P = 0.0008). The perioperative mortality rate was 16.7% in those with COVID-19 compared to 1.4% in COVID-19 negative subjects [aRR = 9.29; 95% confidence interval (CI), 5.68-15.21]. Serious complications were identified in 58.3% of COVID-19 subjects versus 6.0% of controls (aRR = 7.02; 95%CI, 4.96-9.92). Cardiac arrest, sepsis/shock, respiratory failure, pneumonia, acute respiratory distress syndrome, and acute kidney injury were more common in those with COVID-19. The intensive care unit admission rate was 36.1% in those with COVID-19 compared to 16.4% of controls (aRR = 1.34; 95%CI, 0.86-2.09). Conclusions COVID-19 is associated with an increased risk for serious perioperative morbidity and mortality. A substantial number of patients with COVID-19 are not identified until after surgery.
Academic Startups: Best Practices for Innovation and High Impact Student Experiences

The authors developed the Elements of Academic Startups Taxonomy to illustrate the main practices and values used to establish the student operated facilities SPARKS, a cafe, and Innovate 1858, a lifestyle boutique. The values of innovation and high-impact student experiences guided each decision in developing both realistic retail learning laboratories in the Student Innovation Center at Iowa State University.
How did the situation at the Queensway–Carleton get so nasty?

“No cap on babies” read the placard of a demonstrator marching outside Ottawa's Queensway–Carleton Hospital last fall. The marchers, who included 4 of the hospital's 7 obstetricians, were outraged by the 201-bed community hospital's attempt to cap the number of deliveries in its birthing
Measuring the impact of information systems on organizational behavior

Information systems design’s traditional concentration on short-term, readily quantifiable functional factors has resulted in the development of systems that are usually quite capable of manipulating data in the desired manner to produce the required output, but often fail to promote the general behavioral climate objectives of the organization. Failure to consider such behavioral objectives in the design process can result in information systems that have an impact on the organization that is intrusive in nature. To design information systems that not only meet functional objectives, but also promote objectives related to the organization’s behavior, their impact on organizational behavior must be understood and quantified. Toward that end, a methodology that can measure the impact of an information system has on the behavioral climate of the organization has been developed and tested. Utilizing preand post-implementation assessments of an organization’s behavioral climate, this methodology enables information systems developers to identify specific potential design criteria which, when implemented, will increase the degree to which the organization’s behavioral goals and objectives are met. Consideration of such organizational behavior goals and
Prolactin induces tuberoinfundibular dopaminergic neurone differentiation in Snell dwarf mice if administered beginning at 3 days of age.

The hypothalamic tuberoinfundibular dopaminergic (TIDA) neurones secrete dopamine, which inhibits prolactin secretion. TIDA neurone numbers are deficient in Ames (df/df) and Snell (dw/dw) dwarf mice, which lack prolactin, growth hormone and thyroid-stimulating hormone. Prolactin therapy initiated before 21 days maintains normal-sized TIDA neurone numbers in df/df mice and, when initiated as early as 7 days, maintains the maximum TIDA neurone numbers observed in dw/dw development, which are decreased compared to those in normal mice. The present study investigated the effect of prolactin dose and species on TIDA neurone development. Snell dwarf and normal mice were treated with saline, 5 μg of ovine prolactin (oPRL), 50 μg of oPRL, or 50 μg of recombinant mouse prolactin (rmPRL) beginning at 3 days of age. Brains were analysed at 45 days using catecholamine histofluorescence, and immunohistochemistry for tyrosine hydroxylase or bromodeoxyuridine. Normal mice had greater (P ≤ 0.01) TIDA neurones than dw/dw, regardless of treatment. TIDA neurones in 50 μg oPRL-treated dw/dw mice were greater (P ≤ 0.05) than those in 5 μg oPRL- and rmPRL-treated dw/dw mice, which were greater (P ≤ 0.01) than those in saline-treated dw/dw mice. Fifty microgram oPRL-treated dw/dw mice also had greater (P < 0.01) TIDA neurone numbers than the maximum numbers observed in untreated dw/dw mice development. Among saline, 5 μg oPRL and 50 μg oPRL treatments, but not rmPRL, A14 neurone numbers were higher (P ≤ 0.01) in normal compared to in dw/dw mice. The mechanism of TIDA neurone recruitment was investigated using bromodeoxyuridine (BrdU) treatment at intervals after 21 days. Mice treated with rmPRL, but not oPRL, had increased BrdU incorporation in the periventricular area surrounding the third ventricle and median eminence and in the arcuate nucleus. The data obtained in the present study indicate that oPRL, but not rmPRL, when given at a high enough dose, induces TIDA neurone differentiation in dw/dw mice. This supports neurotrophic effects of prolactin on TIDA neurones in early postnatal development that extends beyond maintenance of the cell population.
History of Childhood Maltreatment, Negative Cognitive Styles, and Episodes of Depression in Adulthood

Participants at high (HR) and low (LR) cognitive risk for depression, based on the presence versus absence of negative cognitive styles, were followed longitudinally for 2.5 years. Reported levels of childhood emotional, but not physical or sexual, maltreatment were related to levels of hopelessness and episodes of nonendogenous major depression (NE-MD) and hopelessness depression (HD) during the prospective follow-up period. HR participants reported more childhood emotional maltreatment but less childhood physical maltreatment than did LR participants. In support of Beck's (1967, 1987) theory, cognitive risk fully mediated the relation between childhood emotional maltreatment and NE-MD. In support of the hopelessness theory (Abramson, Metalsky, & Alloy, 1989), cognitive risk partially mediated the relation between childhood emotional maltreatment and hopelessness and fully mediated the relation between childhood emotional maltreatment and HD. Additionally, hopelessness partially mediated the relation between cognitive risk and HD.
The Right to Strike and its Possible Conflict with Other Fundamental Rights of the People in the United States

Although the right to strike is not constitutionally protected in the U.S., it is protected for private sector workers under Section 7 of the National Labor Relations Act as concerted activity for mutual aid and protection. Federal employees and most state and local government employees do not have the right to strike, but several states permit work stoppages by non-essential personnel. Most collective bargaining agreements contain no-strike clauses forbidding work stoppages during the term of such contracts. Sympathy strikes by private sector workers supporting strikes by employees bargaining over new contract terms are usually protected as concerted activity for mutual aid, Secondary strikes by the employees of secondary firms doing business with the primary companies invovled in labor disputes are generally forbidden under Section 8(b)(4) of the NLRA. Slow-down and sit-down work stoppages are not unlawful per se, but are unprotected activities that may lead to worker terminations due to the inappropriate disloyalty shown toward the affected employers. Strikes designed to organize employees or to obtain bargaining recognition from target employers are severely restricted under Section 8(b)(7) of the NLRA.
Using low-cost MEMS accelerometers and gyroscopes as strapdown IMUs on rolling projectiles

Low-cost, micromachined, inertial sensors have been steadily emerging into the commercial marketplace. Some of these commercial off-the-shelf (COTS) sensors were evaluated for their insertion potential into military applications such as test and evaluation (T&E) and smart munition guidance. Performance requirements to provide time, space, position, and attitude information (TSPAI) and allow for navigation capabilities are fast approaching those needed, especially when integrated with a global positioning system (GPS) receiver. Artillery projectiles and rockets, instrumented with commercially available low-cost microelectromechanical systems (MEMS) accelerometers, spin sensors, and custom telemetry units, have been flight tested with good success. Test results suggest that many of these sensors are rugged enough for launch survivability and subsequent operation. Analysis of the accelerometer flight data shows good agreement with ground-based radar and other truth measurements. Ground tests of a MEMS gyroscope on a ballistic flight simulator have also been conducted. The results show promise for directly measuring a projectile's pitching and yawing behavior. This paper will present some of the test results and describe the challenges far using these devices as strapdown inertial measurement units (IMUs) on rolling projectiles.
Packed capillary liquid chromatography/electrospray ionization/mass spectrometry in the pharmaceutical sciences: Characterization of protein mixtures

The coupling of packed capillary liquid chromatography with electrospray ionization mass spectrometry has yielded an instrument capable of generating molecular weight information from very complex natural protein mixtures. The use of the packed capillary liquid chromatography columns offers two principle advantages over conventional liquid chromatography columns: high separation efficiencies and very low mobile phase flow rates (100 nL min−1). The low mobile phase flow rates permit the use of a relatively high ionic strength buffer (0.1% trifluoroacetic acid), While delivering a very low mass flux of the buffer to the mass spectrometer.
When dissolved is not truly dissolved—The importance of colloids in studies of metal sorption on organic matter

Abstract In controlled metal sorption experiments, the equilibrium distribution coefficient is a key variable quantifying sorbate partitioning across the solid–solution interface. Separation of metals into ‘dissolved’ and ‘particulate’ fractions is commonly achieved with syringe filtration, where the boundary is somewhat arbitrarily dictated by the limited selection of available pore sizes. Investigations involving natural organic matter, such as bacterial cells or plant tissues, are especially prone to experimental artifacts if the substrate releases abundant colloidal compounds that contribute to sorption by binding free metal cations in a pH-dependent fashion yet pass through conventional filters, causing the truly dissolved fraction to be grossly overestimated. We observed this phenomenon during a study of lanthanide sorption on a marine macroalga, Ulva lactuca, as a function of pH. At low ionic strength, distribution coefficients calculated for a 0.22-μm size cutoff falsely imply that metal sorption reverses to gradual release above pH 4.6, instead of continuing to increase. Centrifuging the filtrates in Amicon® Ultra units (30 and 3 kDa molecular weight cutoff) revealed a mounting proportion of colloid-bound metal, constituting up to 95% of the ‘dissolved’ (
Cyclotides, a promising molecular scaffold for peptide‐based therapeutics

Cyclotides are a new emerging family of large plant-derived backbone-cyclized polypeptides (approximately 30 amino acids long) that share a disulfide-stabilized core (three disulfide bonds) characterized by an unusual knotted structure. Their unique circular backbone topology and knotted arrangement of three disulfide bonds make them exceptionally stable to thermal, chemical, and enzymatic degradation compared to other peptides of similar size. Currently, more than 100 sequences of different cyclotides have been characterized, and the number is expected to increase dramatically in the coming years. Considering their stability and biological activities like anti-HIV, uterotonic, and insecticidal, and also their abilities to cross the cell membrane, cyclotides can be exploited to develop new stable peptide-based drugs. We have recently demonstrated the intriguing possibility of producing libraries of cyclotides inside living bacterial cells. This opens the possibility to generate large genetically encoded libraries of cyclotides that can then be screened inside the cell for selecting particular biological activities in a high-throughput fashion. The present minireview reports the efforts carried out toward the selection of cyclotide-based compounds with specific biological activities for drug design.
Silver sulfide nanoparticle assembly obtained by reacting an assembled silver nanoparticle template with hydrogen sulfide gas

A fast, simple procedure is described for obtaining an assembly of silver sulfide nanoparticles (Ag2S NPs) on a glass substrate through reaction of a template of an assembled layer of silver nanoparticles (Ag NPs) with hydrogen sulfide (H2S) gas. The Ag NP template was prepared by assembling a monolayer of spherical Ag NPs (mean diameter of 7.4 nm) on a polyethylenimine-treated glass substrate. Exposure to pure H2S for 10 min converted the Ag NPs of the template to Ag2S NPs. The resulting Ag2S NP assembly, which retains the template nanostructure and particle distribution, was characterized by optical absorption spectroscopy, atomic force microscopy, transmission electron microscopy (TEM), scanning high resolution TEM, energy dispersive x-ray spectroscopy and x-ray photoelectron spectroscopy. The Ag2S NPs have a crystal structure of monoclinic acanthite, and while they retained the spherical shape of the original Ag NPs, their mean particle size increased to 8.4 nm due to changes to the crystal structure when the Ag NPs are converted into Ag2S NPs. The measured optical absorption edge of the Ag2S NP assembly indicated an indirect interband transition with a band gap energy of 1.71 eV. The Ag2S NP assembly absorbed light with wavelengths below 725 nm, and the absorbance increased monotonically toward the UV region.
Biometric zoos: Theory and experimental evidence

Several studies have shown the existence of biometric zoos. The premise is that in biometric systems people fall into distinct categories, labeled with animal names, indicating recognition difficulty. Different combinations of excessive false accepts or rejects correspond to labels such as: Goat, Lamb, Wolf, etc. Previous work on biometric zoos has investigated the existence of zoos for the results of an algorithm on a data set. This work investigates biometric zoos generalization across algorithms and data sets. For example, if a subject is a Goat for algorithm A on data set X, is that subject also a Goat for algorithm B on data set Y? This paper introduces a theoretical framework for generalizing biometric zoos. Based on our framework, we develop an experimental methodology for determining if biometric zoos generalize across algorithms and data sets, and we conduct a series of experiments to investigate the existence of zoos on two algorithms in FRVT 2006.
Visualizing Release of Single Fluorophores at Membrane Fusion Sites

SNARE proteins play a central role in nearly all intracellular fusion reactions; fusion is driven by formation of trans-SNARE complexes (SNAREpins) through pairing of vesicle-associated v-SNAREs with complementary t-SNAREs on target membranes. We recently reported a docking and fusion assay in which single small unilamellar vesicles containing the synaptic/exocytic v-SNAREs VAMP/synaptobrevin (v-SUVs) fuse rapidly with planar, supported bilayers containing the synaptic/exocytic t-SNARE syntaxin-SNAP25 (t-SBLs), with single fusion events occurring in ∼130 ms after docking. We optimized acquisition conditions such that now the release of single fluorescently labeled lipids can be visualized. As the fluorophores diffuse away from the release site, individual spots become discernible and can be tracked with ∼16 ms resolution. More than 90% of the tracked spots bleach in a single step, strongly suggesting they represent single fluorescent lipid molecules. Intensity-drops as spots disappear follow a normal distribution whose mean defines the intensity of a single fluorophore. This allows us to estimate the total number of lipids in a vesicle prior to its fusion with the t-SBL, given the label density. An independent estimate of vesicle size is based on extrapolating the number of surviving spots as a function of time to just before fusion.We studied the effects of lipid composition. In bilayers containing nearly physiological amounts of cholesterol, the mean squared displacement of single fluorescent lipids that are released into the t-SBL increases linearly in time indicating a diffusive process and yields a diffusion coefficient of ∼0.3 µm2/s, a value that is similar to those found for lipid diffusivities in the plasma membrane of live cells. In addition, the majority of the vesicles that dock end up fusing. In contrast, in bilayers devoid of cholesterol, lipid diffusion is much faster, but only 40-50% of docked vesicles fuse.
Interaction potential between cranberry juice and warfarin

Purpose. The interaction potential between warfarin and cranberry juice is discussed. Summary. Reports from the United Kingdom have raised concern over the interaction potential between cranberry juice and warfarin. Warfarin is the most commonly prescribed oral medication for anticoagulation therapy. Cranberry juice is a flavonoid, which has been shown to induce, inhibit, or act as a substrate for the biosynthesis of several cytochrome P-450 (CYP) isoenzymes. Specifically, cranberry juice may inhibit the activity of CYP2C9, the primary isoenzyme involved in the metabolism of S- warfarin. A search of the medical literature identified three peer-reviewed case reports and two peer-reviewed, prospective, randomized, placebo-controlled clinical trials using metabolic surrogates of warfarin (flurbiprofen and cyclosporine) that described possible interactions between cranberry juice and warfarin. Two case reports suggested that cranberry juice increased the International Normalized Ratio (INR) of patients taking warfarin, but neither clearly identified cranberry juice as the sole cause of INR elevation. One case report appeared to show a correlation between the effects of cranberry juice and warfarin metabolism. Both clinical trials indicated the lack of an interaction between cranberry juice and CYP isoenzymes 2C9 and 3A, both of which are necessary in warfarin metabolism. More studies are required to determine the potential interaction between cranberry juice and warfarin. Conclusion. The available data do not seem to show a clinically relevant interaction between cranberry juice and warfarin; however, patients taking warfarin with cranberry juice should be cautioned about the potential interaction and monitored closely for INR changes and signs and symptoms of bleeding.
Inactivation studies of angiotensin II by purified enzymes

Die hochgereinigte Arylamidase vom Schweinehirn spaltet, im Gegensatz zur ebenfalls isolierten Saureprotease und Aminopeptidase, Ile5-Angiotensin II, wobei die ersten 5 N-terminalen Aminosauren von hydrolytischen Enzymen freigesetzt werden.
Photometric determination of arsenic in silicate rocks

The method described consists in decomposing the silicate rock sample by fusion with sodium hydroxide or sodium hydroxide-peroxide, leaching the melt with water, evolving arsine from the filtrate, and finally determining arsenic by photometric evaluation of molybdenum blue. Satisfactory accuracy has been demonstrated for the range 0.0 to 20 p. p. m. As, for which the method is particularly intended.
Possible relationships between the physical environment and human hypertension: cadmium and hard water

Abstract There is no proven relationship between the physical environment and the pathogenesis of essential hypertension. There are, however, marked and unexplained variations in death rates from cardiovascular disease in the United States. Potable water, an environmental influence to which all persons are exposed, also varies considerably in its hardness and this hardness is inversely correlated with cardiovascular death rates. Experimentally, chronic feeding of cadmium, and perhaps mercury to rats in trace quantities can cause a mild to marked elevation of blood pressure which has been associated with increased mortality. This metal-induced hypertension in animals resembles essential hypertension in man in that there are no other evidences of metal exposure, and it raises the possibility that some clinical hypertension might be related to inapparent metal exposure which in turn might be a function of water hardness.
Astrocyte plasticity revealed by adaptations to severe proteotoxic stress

Neurodegeneration is characterized by an accumulation of misfolded proteins in neurons. It is less well appreciated that glia often also accumulate misfolded proteins. However, glia are highly plastic and may adapt to stress readily. Endogenous adaptations to stress can be measured by challenging stressed cells with a second hit and then measuring viability. For example, subtoxic stress can elicit preconditioning or tolerance against second hits. However, it is not known if severe stress that kills half the population can elicit endogenous adaptations in the remaining survivors. Glia, with their resilient nature, offer an ideal model in which to test this new hypothesis. The present study is the first demonstration that astrocytes surviving one LC50 hit of the proteasome inhibitor MG132 were protected against a second MG132 hit. ATP loss in response to the second hit was also prevented. MG132 caused compensatory rises in stress-sensitive heat shock proteins. However, stressed astrocytes exhibited an even greater rise in ubiquitin-conjugated proteins upon the second hit, illustrating the severity of the proteotoxicity and verifying the continued impact of MG132. Despite this stress, MG132-pretreated astrocytes were completely prevented from losing glutathione with the second hit. Furthermore, inhibiting glutathione synthesis rendered astrocytes sensitive to the second hit, unmasking the cumulative impact of two hits by removal of an endogenous adaptation. These findings suggest that stressed astrocytes become progressively harder to kill by virtue of antioxidant defenses. Such plasticity may permit astrocytes under severe stress to better support neurons and help explain the protracted nature of neurodegeneration.
Space/time statistics of the turbulence in a tokamak edge plasma

The results of a study of the statistical space/time properties of the turbulence observed in the edge region of the Pretext tokamak are reported. A local estimate of the wavenumber frequency spectra S(κ,ω) for poloidal (ky)an d toroidal (kz) wavenumbers is determined for the range 0.5 cm−1 < k < 7.5 cm−1, for both potential and density fluctuations obtained from spatially fixed Langmuir probe pairs. The S(ky, ω) spectra aredominated by low frequencies ( < 200 kHz) and small wavenumbers (< 3 cm−1) and appear broadened about an approximately linear statistical dispersion relation, (ω). The broadening is characterized by a spectral width σk (ω) (root-mean-square deviation about (ω)) which is of the order of (ω). The turbulence appears to propagate poloidally with an apparent mean phase velocity of (1–2) × 105 cms−1 in the ion diamagnetic drift direction. Measurements of the fluctuation-induced particle transport reveal the particle flux to be outward and resulting primarily from the low-frequency, long-wavelength components of the turbulence. A particle diffusion coefficient Dx, estimated from the measured particle flux and density profiles, is of the order of the coefficient estimated for Bohm diffusion, but appears to increase with density.
Loci of competition for future internet architectures

Designing for competition is an important consideration for the design of future Internet architectures. Network architects should systematically consider the loci of competition in any proposed network architecture. To be economically sustainable, network architectures should encourage competition within each locus, anticipate and manage the interactions between the loci, and be adaptable to evolution in the loci. Given the longevity of network architectures relative to network technologies and applications, it is important to ensure that competition is not unnecessarily foreclosed at any particular locus of competition.
Extent of extracranial disease is a powerful predictor of survival in patients with brain metastases from gynecological cancer

Central nervous system metastasis from gynecological malignancy is a rare phenomenon that has been described in the past 30 years. The objective of this study is to analyze the treatment modalities and prognostic factors for brain metastases from gynecological tumors that predict prolonged survival. A retrospective chart and pathology review of 47 patients diagnosed with a gynecological tumor with brain metastasis in 1994–2004 was performed. Thirty patients had undergone initial diagnosis and treatment at our institution, and 17 patients were referred following primary treatment at an outside institution. Adjusted Chi-square, Kaplan–Meier survival estimates, log-rank tests, and Cox regression analysis were utilized for statistical analysis of the total cohort. Of the 3146 patients with newly diagnosed gynecological cancer in this 10-year period, 30 developed brain metastasis demonstrating an incidence of 0.95%. Overall median survival from the time of diagnosis of brain metastasis was 7.5 months (95% CI 4–15, range 9 days–64 months) and 40% survival at 1 year. Multivariate analysis revealed evidence of extracranial disease at time of metastasis diagnosis predicted decreased survival (hazard ratio 6.207), while papillary serous histology (hazard ratio 0.42), and use of any chemotherapy (hazard ratio 0.24) predicted longer survival. No other patient or tumor characteristics were found to be independent prognostic indicators affecting survival. Despite the ominous prognosis associated with the development of brain metastasis, these retrospective data suggest that multimodal therapy with whole brain radiation therapy, chemotherapy, and surgical resection of metastases in selected patients without evidence of extracranial and with solitary or multiple lesions can prolong survival.