cssi/SciSciGPT-SciSciNet huggingface dataset:
Effect of administration method, animal weight and age on the intranasal delivery of drugs to the brain

Abstract Background The intranasal route of administration has proven to be an effective method for bypassing the blood brain barrier and avoiding first pass hepatic metabolism when targeting drugs to the brain. Most small molecules gain rapid access to CNS parenchyma when administered intranasally. However, bioavailability is affected by various factors ranging from the molecular weight of the drug to the mode of intranasal delivery. Comparison with existing methods We examined the effects of animal posture, intranasal application method and animal weight and age on the delivery of radiolabeled pralidoxime (3H-2-PAM) to the brain of rats. Results We found that using upright vs. supine posture did not significantly affect 3H-2-PAM concentrations in different brain regions. Older animals with higher weights required increased doses to achieve the same drug concentration throughout the brain when compared to young animals with lower body weights. The use of an intranasal aerosol propelled delivery device mainly increased bioavailability in the olfactory bulbs, but did not reliably increase delivery of the drug to various other brain regions, and in some regions of the brain delivered less of the drug than simple pipette administration. Conclusion In view of the emerging interest in the use of intranasal delivery of drugs to combat cognitive decline in old age, we tested effectiveness in very old rats and found the method to be as effective in the older rats.
SEASONAL ABUNDANCE OF RED AND GREEN MORPHS OF THE TOBACCO APHID (HOMOPTERA: APHIDIDAE) ON FLUE-CURED TOBACCO IN GEORGIA

The seasonal abundance of red and green morphs of the tobacco aphid, Myzus nicotianae Blackman, was investigated on flue-cured tobacco in Georgia during 1987–1988. The effect of tobacco transplantation date also was examined in 1988. Aphid populations peaked on tobacco in mid-June 1987, then rapidly declined following the removal of the terminal floral branch (topping). Early season samples contained both green and red morphs; however, by early June, and throughout the remainder of the season, the aphid population was almost exclusively comprised of the red morph. Similar results were obtained in 1988, although population densities were higher and peaked earlier in the early transplanting (30 March) compared to the 14 April and 28 April transplantings. Regardless of transplanting date, the red morphs began a rapid population increase about 45 days after transplantation, and this increase continued until plants were topped. Daily high temperatures exceeding 35°C did not appear detrimental to the red morphs...
OR15 Hierarchy of HLA types in provoking antibody production following kidney transplantation

Aim HLA antigens are diverse in cell surface expression, peptide presentation, binding immune receptors, and in eliciting immune responses. Here we examined the ability of distinct HLA types in inducing antibody (Ab) production following kidney transplantation (Ktx). Methods A cohort of 308 candidates (44% female) waiting for 2nd Ktx was studied. Prior to 1st Ktx, all were negative for HLA Abs by One Lambda single antigen bead (OL-SAB) assay. HLA Abs were measured in pre-2nd tx sera using OL-SAB. The strength (mean of MFIs) and frequency of each Abs in pre-2nd tx sera of 308 candidates were determined and plotted. Results A positive linear correlation was observed between Ab strengths to frequency with an r2 = 0.6 and p DQ8 > DQ7 > B76 > DR9 > DQ4 > B45 > DQ6 > B57 > DQ2 > A1 > DQ5 > DR7 > B57 > B58 > A24 > B49 > DR53 > A2 > B82 > B44 > A96 > A23 > A11 > A68. All HLA-Cw antigens and a subset of DPB antigens (DP15, DP13, DP5, DP1, DP23, DP4) induce Ab production at low levels and low frequency. Within Cw types, the most poorly immunogenic represents to be those carrying C1 epitope that binds to KIR2DL2/L3. The moderate inducer includes most HLA-B, HLA-A and DR antigens, and the hierarchy from the strongest inducer within this group is B7 > A10 > B5 > DR52 > DR51 CREG. The B5 CREG was diverse and observed to have four outliers from the linear fit. The strongest to weakest to trigger Abs in B5 CREG is ordered as follows: B76 > B63 > B73 > B62 > B75 > B78 > B46. Conclusions Our findings categorize 121 HLA types into three hierarchical sets based on their ability in eliciting Ab production following Ktx – strongly immunogenic, moderately immunogenic, and poorly immunogenic. The strongly immunogenic HLA types should be considered for matching in Ktx, while the poorly immunogenic HLA antigens are tolerable.
Piezos thrive under pressure: mechanically activated ion channels in health and disease

Cellular mechanotransduction, the process of translating mechanical forces into biological signals, is crucial for a wide range of physiological processes. A role for ion channels in sensing mechanical forces has been proposed for decades, but their identity in mammals remained largely elusive until the discovery of Piezos. Recent research on Piezos has underscored their importance in somatosensation (touch perception, proprioception and pulmonary respiration), red blood cell volume regulation, vascular physiology and various human genetic disorders.
Chronic Disease Patient Experience of Healthcare Services in Ireland

Chronic disease in Ireland is currently reported by 38% of the adult population. Modern integrated health systems recognise that they need to be proactive and engage citizens to support healthy lifestyles. A consideration of the patient perspective is an important first step in addressing these challenges. The present study conducted a qualitative, thematic analysis of 7 semi-structured interviews with patients, all of whom had a formal diagnosis of one or more chronic diseases. Five themes emerged, which reflect that individuals with chronic disease in Ireland experience high levels of treatment burden and significant challenges managing their disease. Patients report significant psychological effects of managing chronic disease, many of which emerge as a result of poor exchange of information between the patient and healthcare provider. Positive experience of chronic disease management was evident in some interviews and all participants showed resilience and coping associated with disease progression. This study’s findings suggest that health and social care services can be re-organised to meet the often complex needs of patients with chronic disease.
Keith Haring, Felix Gonzalez-Torres, Wolfgang Tillmans, and the AIDS Epidemic: The Use of Visual Art in a Health Humanities Course

Contemporary art can be a powerful pedagogical tool in the health humanities. Students in an undergraduate course in the health humanities explore the subjective experience of illness and develop their empathy by studying three artists in the context of the AIDS epidemic: Keith Haring, Felix Gonzalez-Torres, and Wolfgang Tillmans. Using assignments based in narrative pedagogy, students expand their empathic response to pain and suffering. The role of visual art in health humanities pedagogy is discussed.
Demographic Techniques: Indirect Estimation

Indirect estimation methods have been developed to facilitate measurement of demographic processes in countries lacking accurate conventional data. The methods can be divided into two broad groups. ‘Indirect estimates’ seek to derive measures of demographic parameters from indicators largely, but not entirely, determined by the parameter of interest. The methods adjust the indicator for the influence of other factors to obtain a ‘pure’ measure of the parameter required. ‘Consistency checks’ seek to compare measures of a given process derived from different sources, and, if the measures are found to be inconsistent, to use knowledge of typical error patterns as a basis for adjustment. Although indirect estimation is an interim solution to problems of data quality, it will remain an important element of demographic measurement in developing countries for the foreseeable future.
Elastic Scattering of Particles with Spin

In Sec. 10.1.2 we wrote down the form of the free wave function and of the Green’s functions for particles with arbitrary spin. We now wish to subject them to a partial wave analysis similar to that used in Sec. 11.1.1 for particles of spin 0. For this purpose it is useful to introduce generalizations of the spherical harmonics analogous to the vector spherical harmonics of electromagnetic theory.
Laser Microirradiation and Computer Video Optical Microscopy in Cell Analysis

Laser light is intense, coherent, monochromatic electromagnetic radiation. Because of these properties it can be a unique probe of cellular structure and function. The damage produced by a focused laser beam may be caused by classical absorption by natural or applied chromophores and the subsequent generation of heat (Berns and Salet, 1972), or it may be caused by a photochemical process. An example of such a process would be the production of monoadducts or diadduct cross-linking in the case of laser light’s stimulated binding of psoralens to nucleic acids (Peterson and Berns, 1978a). However, a third possibility is the generation of damage by an uncommon physical effect that occurs when ultra-high photon densities are achieved in very short periods of time (a few nanoseconds or picoseconds). The resulting nonlinear optical effects such as multiphoton absorption occur when the classic law of reciprocity does not hold. These effects may be responsible for some of the disruption observed in biological material (Berns, 1976). Whichever of the above damage-producing mechanisms is operating, be it “classical” or “uncommon,” the damage often can be confined to a specific cellular or subcellular target in a consistent and controllable way. In addition, once the biophysical mechanism of laser interaction with the molecules is ascertained, the investigator has a method for precise disruption of a specific class of molecules within a strictly delimited region of the living cell. The size of this region may be considerably smaller than the size of the focused laser beam because of the distribution of the target molecules in the target zone. However, the size of the focused laser spot also is of paramount importance because it defines the maximum volume of biological material that will be available for direct interaction with the laser photons. Though the diameter of the focused laser spot is a direct function of the wavelength, the magnification of the focusing objective, and the numerical aperture of the objective, the actual diameter of the “effective” lesion area may be considerably less than the theoretical limit of the focused laser beam. This is because a high-quality laser beam can be generated in the TEM∞ mode, which results in a beam with a gaussian energy profile across it. The profile is carried over to the focused spot, which results in a “hot spot” of energy in the center. It has been demonstrated consistently (Berns, 1974a) that by careful attenuation of the raw laser beam, the damage-producing portion in the focused spot can be confined to the central hot spot (e.g., that is the only region within the focused spot that is above the threshold for damage production). As a result, lesions can be routinely produced less than 0.25 μm in diameter, and frequently down to 0.1 μm in diameter.
A generic microgrid controller: Concept, testing, and insights

Abstract Microgrids have garnered attention in recent years as a way to increase the reliability of the grid, increase the reliability of electricity service to customers, adapt to an increasing percentage of intermittent renewable generation, and serve both customer critical loads and the needs of adjacent communities in the case of emergencies such as natural disasters. One barrier to microgrids is the historic cost and lack of standardization associated with microgrid controllers. To reduce this cost and address standardization, specifications for a Generic Microgrid Controller (GMC) were developed with the goal to facilitate the design and ease of adaptation of microgrid controllers to various microgrids of different sizes and with different resources. A GMC must address two core functions, Transition and Dispatch, as well as several optional higher level functions such as economic dispatch, and renewable and load forecasting. The GMC specifications were demonstrated and evaluated using a commercial simulation platform for two different microgrids, a 20 MW-Class community microgrid and a 10 MW-Class medical center microgrid. For each microgrid, the GMC was tested in hardware-in-the-loop (HIL) using an OPAL-RT real-time digital simulator, and the two core functions were assessed. The results established that (1) the GMC is successful in seamlessly transitioning the microgrids to and from an islanded mode, (2) a load/generation mismatch at the time of separation depends on the microgrid configuration and must be lower than a specific value determined by simulation testing, and (3) the GMC Dispatch Function response is acceptable in maintaining, in the islanded mode, 60 Hz for a range of load changes.
Articular cartilage gene expression patterns in the tissue surrounding the impact site following applications of shear and axial loads

Osteoarthritis is a degradative joint disease found in humans and commercial swine which can develop from a number of factors, including prior joint trauma. An impact injury model was developed to deliver in vitro loads to disease-free porcine patellae in a model of OA. Axial impactions (2000 N normal) and shear impactions (500 N normal with induced shear forces) were delivered to 48 randomly assigned patellae. The patellae were then cultured for 0, 3, 7, or 14 days following the impact. Specimens in the tissue surrounding the loading site were harvested and expression of 18 OA related genes was studied via quantitative PCR. The selected genes were previously identified from published work and fell into four categories: cartilage matrix, degradative enzymes, inflammatory response, and apoptosis. Type II collagen (Col2a1) showed significantly lower expression in shear vs. axial adjacent tissue at day 0 and 7 (fold changes of 0.40 & 0.19, respectively). In addition, higher expression of degradative enzymes and Fas, an apoptosis gene, was observed in the shear specimens. The results suggest that a more physiologically valid shear load may induce more damage to surrounding articular cartilage than a normal load alone.
AI Revolution: How Data Can Identify and Shape Consumer Behavior in Ecommerce

Data has become one of the most significant instruments in e-commerce innovation. Benefits to the entire society can be summarized as following: from the government’s perspective - to assess the impact of e-commerce to the economy; for merchants - to understand consumers’ needs; and for consumers - to be offered with the right product he/she is looking for. The digital revolution in the past five years has shown the need to offer more differentiated services than the physical stores, when consumers are not able to try and touch products. It is for this reason that e-commerce has continuously developed and transformed Research Online, Purchase Offline into a true experience. Considering the future of e-commerce is to enhance economic development and growth, this research will discuss the disruption of Research and Development through big data. The core objective of this research is to propose a predictive model to deeply understand consumer behavior by analyzing new regulations and transaction records.
Reliability of self-reported smoking history and its implications for lung cancer screening.

Abstract Clinical guidelines endorse either a 30 or 20 pack-year smoking history threshold when determining eligibility for lung cancer screening (LCS). However, self-reported smoking history is subject to recall bias that can affect patient eligibility. We examined the reliability of smokers’ self-reported tobacco use and its impact on eligibility for LCS. Current or former smokers aged 55–77 years completed questionnaires requesting demographic information and smoking history. Data were collected between December 2014 and September 2015. Total pack-year smoking history was calculated for each participant based on their responses at baseline and one month later. One hundred and two participants completed the study (mean age = 63.6 years). The intraclass correlation coefficient for the pack-year estimate was 0.93. For the 30 pack-year threshold, eight (7.8%) participants were eligible at one but not both assessment periods. For the 20 pack-year threshold, twelve participants (11.8%) were eligible at one but not both assessment periods. Inconsistent reporting was higher among current compared to former smokers. Smokers’ self-reported tobacco use appears highly reliable over short time periods. Nevertheless, there is some inconsistent reporting. We recommend that clinicians carefully assess smoking history, probe patients’ recall of duration and quantity of smoking, and collect tobacco use information at every encounter.
A Holistic Approach for Automatic Deep Understanding and Protection of Technical Documents

A Technical Document (TD) is mainly composed by a set of modalities appropriately structured and associated. These modalities could be NL-text, block diagrams, formulas, tables, graphics, pictures ...
Voles mediate functional trait diversity along a resource gradient

Disentangling the effect of multiple ecological processes on plant trait composition is complicated by the fact that both top‐down and bottom‐up processes may affect similar traits. We examined the interacting role of resource variation and vole herbivory on functional trait patterns in an annual California grassland. We manipulated vole herbivory via exclosures at eight grassland sites along a steep resource gradient and measured plant composition and functional traits over 3 years. Plants with resource acquisitive functional traits were favoured at sites with increasing resources. Vole herbivory influenced community‐weighted mean (CWM) leaf nitrogen (N) and seed mass, suggesting these traits may mediate plant susceptibility to vole herbivory. After 3 years, CWM leaf N increased in the absence of the voles, as did CWM seed mass, although this increase in CWM seed mass only occurred at higher resource sites. Vole exclusion at high‐resources sites also increased the functional diversity of leaf N and seed mass by the end of the experiment. Overall, environmental filtering primarily structured the dominant plant trait strategies, but vole herbivory also influenced the functional diversity of traits that influence herbivore susceptibility, particularly at resource‐rich sites. Thus, habitat filtering and herbivory can operate on different dimensions of plant functional composition to influence the species and functional composition of communities. A free Plain Language Summary can be found within the Supporting Information of this article.
Movement–Media Relations in the Hybrid Media System: A Case Study from the U.S. Transgender Rights Movement

Whereas social movement–media relations were, in the era of mass media, a dialogic relationship of mutual, albeit asymmetric, dependency between news makers and social movement organizations, the h...
Measuring the dynamic response of the thylakoid architecture in plant leaves by electron microscopy.

The performance of the photosynthesis machinery in plants, including light harvesting, electron transport, and protein repair, is controlled by structural changes in the thylakoid membrane system inside the chloroplasts. In particular, the structure of the stacked grana area of thylakoid membranes is highly dynamic, changing in response to different environmental cues such as light intensity. For example, the aqueous thylakoid lumen enclosed by thylakoid membranes in grana has been documented to swell in the presence of light. However, light-induced alteration of the stromal gap in the stacked grana (partition gap) and of the unstacked stroma lamellae has not been well characterized. Light-induced changes in the entire thylakoid membrane system, including the lumen in both stacked and unstacked domains as well as the partition gap, are presented here, and the functional implications are discussed. This structural analysis was made possible by development of a robust semi-automated image analysis method combined with optimized plant tissue fixation techniques for transmission electron microscopy generating quantitative structural results for the analysis of thylakoid ultrastructure. Significance statement A methodical pipeline ranging from optimized leaf tissue preparation for electron microscopy to quantitative image analysis was established. This methodical development was employed to study details of light-induced changes in the plant thylakoid ultrastructure. It was found that the lumen of the entire thylakoid system (stacked and unstacked domains) undergoes light-induced swelling, whereas adjacent membranes on the stroma side in stacked grana thylakoid approach each other.
POGLUT2 and POGLUT3 O-glucosylate multiple EGF repeats in fibrillin-1, -2, and LTBP1 and promote secretion of fibrillin-1.

Fibrillin-1 (FBN1) is the major component of extracellular matrix microfibrils, which are required for proper development of elastic tissues, including the heart and lungs. Through protein–protein interactions with latent transforming growth factor (TGF) β-binding protein 1 (LTBP1), microfibrils regulate TGF-β signaling. Mutations within the 47 epidermal growth factor-like (EGF) repeats of FBN1 cause autosomal dominant disorders including Marfan Syndrome, which is characterized by disrupted TGF-β signaling. We recently identified two novel protein O-glucosyltransferases, Protein O-glucosyltransferase 2 (POGLUT2) and 3 (POGLUT3), that modify a small fraction of EGF repeats on Notch. Here, using mass spectral analysis, we show that POGLUT2 and POGLUT3 also modify over half of the EGF repeats on FBN1, fibrillin-2 (FBN2), and LTBP1. While most sites are modified by both enzymes, some sites show a preference for either POGLUT2 or POGLUT3. POGLUT2 and POGLUT3 are homologs of POGLUT1, which stabilizes Notch proteins by addition of O-glucose to Notch EGF repeats. Like POGLUT1, POGLUT2 and 3 can discern a folded versus unfolded EGF repeat, suggesting POGLUT2 and 3 are involved in a protein folding pathway. In vitro secretion assays using the N-terminal portion of recombinant FBN1 revealed reduced FBN1 secretion in POGLUT2 knockout, POGLUT3 knockout, and POGLUT2 and 3 double-knockout HEK293T cells compared with wild type. These results illustrate that POGLUT2 and 3 function together to O-glucosylate protein substrates and that these modifications play a role in the secretion of substrate proteins. It will be interesting to see how disease variants in these proteins affect their O-glucosylation.
Can EBRT Dose-Escalation Above 80 Gy Yield Comparable Survival Rates Relative to EBRT Plus Brachytherapy Boost in Men With Unfavorable Intermediate-Risk Prostate Cancer?

PURPOSE/OBJECTIVE(S) Current recommendations regarding radiotherapy treatment for unfavorable intermediate-risk prostate cancer (UIR-PCa) include external beam radiotherapy (EBRT) ± brachytherapy boost (BT) ± androgen deprivation therapy (ADT). Dose-escalated EBRT ± ADT is associated with excellent long-term outcomes, but ERBT+BT ± ADT can achieve higher dose escalation beyond what can be achieved with EBRT alone. Prior studies have shown improved biochemical control and reduced distant metastasis with EBRT+BT vs. EBRT in men with intermediate-risk disease, but it is unclear if this translates into a survival benefit. MATERIALS/METHODS Men with UIR-PCa diagnosed between 2004 and 2015 and treated with EBRT ± ADT or EBRT+BT ± ADT were identified in the National Cancer Database (NCDB). EBRT was delivered with conventional fractionation (≥ 72 Gy in 1.8-2.0 Gy per fraction), while EBRT+BT was defined as patients receiving EBRT to a total dose of 40-50.4 Gy plus high-dose rate or low-dose rate brachytherapy. Patients with a Charlson-Deyo comorbidity index (CDCI) score > 1, who received systemic therapy other than ADT, or missing key information were excluded. Propensity-weighted multivariable analysis (MVA) using Cox regression modeling was used to compare overall survival (OS) hazard ratios. Covariables included age, race, ethnicity, year of diagnosis, CDCI score, insurance status, educational and socioeconomic metrics, treatment at an academic center, PSA at diagnosis, Gleason score, clinical T-stage, and receipt of ADT. RESULTS The study cohort included 32,246 unfavorable intermediate-risk prostate cancer patients treated with: (i) EBRT (n = 13,265), (ii) EBRT+ADT (n = 13,123), (iii) EBRT+BT (n = 3,440), or (iv) EBRT+BT+ADT (n = 2,418). Cumulative doses of EBRT ± ADT are summarized in Table 1. The average time to follow-up was 62 months (standard deviation ± 39 months). Propensity-weighted MVA showed that EBRT+BT ± ADT was associated with improved OS relative to increasing doses of EBRT ± ADT. However, the OS benefit associated with EBRT+BT ± ADT diminished as the cumulative dose of radiation in the EBRT ± ADT cohort increased (Table 1). CONCLUSION The addition of brachytherapy to EBRT correlated with reduced mortality in men with UIR prostate cancer, including patients treated with EBRT ± ADT to ≥80 Gy. The relative OS benefit associated with EBRT+BT declined as the radiation dose increased in the EBRT ± ADT cohort.
Training in Clinical Psychology in the United States: Practitioner Model

The National Council of Schools and Programs of Professional Psychology's practitioner-scholar model for education and training in professional psychology appeared in 1997 and 2010 (Peterson et al.) with five central components. Many elements of the five components are updated from their original presentations: (1) broadened view of psychology with a flexible epistemology, multiple ways of knowing, and an articulation of how practitioners doing practice remain ‘local clinical scientists’ doing ‘disciplined inquiry’; (2) integrative pedagogy; (3) competency-based core curriculum integrating practical and scientific knowledge, skills, and attitudes, now including diversity; (4) elements of practice, including multiple roles, the self of the psychologist and reflective practice, practicum and internship training, and systematic evaluation; and (5) the social nature of professional psychology and its social responsibility, including an appreciation of ethnic and racial diversity, and gender. The impetus for the practitioner-scholar model and the critiques of the professional psychology movement are briefly mentioned.
Efficacies of designer biochars in improving biomass and nutrient uptake of winter wheat grown in a hard setting subsoil layer

In the Coastal Plains region of the United States, the hard setting subsoil layer of Norfolk soils results in low water holding capacity and nutrient retention, which often limits root development. In this region, the Norfolk soils are under intensive crop production that further depletes nutrients and reduces organic carbon (C). Incorporation of pyrolyzed organic residues or ‘‘biochars’’ can provide an alternative recalcitrant C source. However, biochar quality and effect can be inconsistent and different biochars react differently in soils. We hypothesized that addition of different designer biochars will have variable effects on biomass and nutrient uptake of winter wheat. The objective of this study was to investigate the effects of designer biochars on biomass productivity and nutrient uptake of winter wheat (Triticum aestivum L.) in a Norfolk’s hard setting subsoil layer. Biochars were added to Norfolk’s hard setting subsoil layer at the rate of 40 Mg ha � 1 . The different sources of biochars were: plant-based (pine chips, PC); animal-based (poultry litter, PL); 50:50 blend (50% PC:50% PL); 80:20 blend (80% PC:20% PL); and hardwood (HW). Aboveground and belowground biomass and nutrient uptake of winter wheat varied significantly (p 6 0:0001) with the different designer biochar applications. The greatest increase in the belowground biomass of winter wheat over the control was from 80:20 blend of PC:PL (81%) followed by HW (76%), PC (59%) and 50:50 blend of PC:PL (9%). However, application of PL resulted in significant reduction of belowground biomass by about 82% when compared to the control plants. The average uptake of P, K, Ca, Mg, Na, Al, Fe, Cu and Zn in both the aboveground and belowground biomass of winter wheat varied remarkably with biochar treatments. Overall, our results showed promising significance for the treatment of a Norfolk’s hard setting subsoil layer since designer biochars did improve both aboveground/belowground biomass and nutrient uptake of winter wheat. Published by Elsevier Ltd.
102 – Pregnancy—Success or Failure: The Influence of Autoimmune Diseases

Autoimmune disease is known to be associated with infertility; increased fetal wastage; and significant fetal and neonatal pathology, which may be a consequence of transplacental passage of maternal immunoglobulin. This chapter discusses in detail how maternal autoimmune disease can prevent or disrupt pregnancy. Autoimmune disease can also produce transient or permanent pathology in offspring, which is sometimes influenced by as-yet-unknown fetal and maternal factors. Pregnancy may exacerbate or ameliorate maternal clinical autoimmune disease, but its benefits are typically temporary with the disease flaring in the postpartum period. Reports suggest to consider that pregnancy might even contribute to the pathogenesis of autoimmune disease. Studies suggest that microchimerism may play a role in the pathogenesis of systemic sclerosis, autoimmune thyroid disease, and even multiple sclerosis.
Studies of the arterial pulse wave. I. The normal pulse wave and its modification in the presence of human arteriosclerosis.

Abstract 1. 1. A sensitive instrument for the recording of arterial pulse waves is described. It is tentatively designated as a Vasculograph. 2. 2. The characteristics of the normal arterial pulse wave contour, as recorded by this instrument, are reported. The accuracy of the recordings has been demonstrated by the similarity of simultaneous intra- and extraarterial tracings. 3. 3. The changes in configuration of the arterial pulse wave in the presence of clinical evidences of arteriosclerosis appear to be diminution to disappearance of the dicrotic wave. The accuracy of this finding has also been demonstrated by simultaneous intra- and extraarterial recordings. 4. 4. The implications of the disappearance of the dicrotic wave in the presence of clinical evidences of arteriosclerosis are discussed.
Multiple subspace ULV algorithm and LMS tracking

Publisher Summary The Least Mean Squares (LMS) adaptive algorithm is the most popular algorithm for adaptive filtering because of its simplicity and robustness. However, its main drawback is slow convergence whenever the adaptive filter input auto-correlation matrix is ill-conditioned that is, the eigenvalue spread of this matrix is large. The goal of this chapter is to develop an adaptive signal transformation which can be used to speed up the convergence rate of the LMS algorithm, and at the same time provide a way of adapting only to the strong signal modes, in order to decrease the excess Mean Squared Error (MSE). It uses a data dependent signal transformation. The algorithm tracks the subspaces corresponding to clusters of eigenvalues of the auto-correlation matrix of the input to the adaptive filter, which have the same order of magnitude. The algorithm up-dates the projection of the tap weights of the adaptive filter onto each subspace using LMS algorithms with different step sizes. The technique also permits adaptation only in those subspaces, which contain strong signal components leading to a lower excess MSEas compared to traditional algorithms. The transform should also be able to track the signal behavior in a non-stationary environment. The chapter develops such a data adaptive transform domain LMS algorithm, using a generalization of the rank revealing ULV decomposition.
Composition of Sow Milk During Lactation

The composition of sow colostrum and milk was quantitated in 25 sows at 14 time points throughout lactation. All animals belonged to the same experimental herd of German Landrace, farrowed within 4 d, and were of various lactation numbers and various litter sizes. In the first 6 h of lactation colostrum total solids (TS) and protein contents were higher, while fat and lactose contents were lower than in mature milk. Decreased total protein and whey protein contents and concomitantly increased fat and lactose content, with nearly unchanged TS levels, indicate transition from colostrum to mature milk. The high protein content of colostrum was largely due to immunoglobulin (Ig). During the first 6 h, IgG accounts for nearly all the protein in colostrum but plays a decreasing role in sow milk as lactation proceeds. After 2 wk, IgA levels begin to increase and at the end of lactation, IgA constitutes 40% of the total whey protein. No influences of lactation number and litter size on milk composition could be ascertained in this study.
Control of Discrete Event Systems Modeled with Deterministic Buchi Automata

Ramadge and Wonham have established a control theory of DES modeled by state machines. Previous work by Ramadge extended the concept of controllable languages to infinite languages and presented conditions for the existence of a supervisor for systems modeled by Buchi automata. This paper derives requirements for the existence of a supervisor under less restrictive conditions on the constraint language for plants which satisfy certain conditions. This supervisor approaches the prescribed closed loop behavior and retains all behaviors within a specified error bound of the desired behavior. Both deterministic and non-deterministic supervisors are considered. The construction for such a supervisor is given in an example.
Micro thermoelectric cooler fabrication: growth and characterization of patterned Sb/sub 2/Te/sub 3/ and Bi/sub 2/Te/sub 3/ films

A column-type micro thermoelectric cooler is being fabricated using p-type Sb/sub 2/Te/sub 3/ and n-type Bi/sub 2/Te/sub 3/ films (approximately 4 /spl mu/m thick). The films are grown by thermal co-evaporation and patterned on Cr/Au/Ti/Pt (hot) connectors, which are deposited onto a silicon dioxide coated wafer. The column height is limited by control of the Te deposition rate. Although a high substrate temperature during thermoelectric film deposition is desired, it has been limited by the degradation of the photoresist used for patterning. The measured Seebeck coefficient and electrical resistivity of the thermoelectric films are reported, and preliminary results show that excess tellurium increases the Seebeck coefficient.
Characterization of the cyclophilin gene family of Arabidopsis thaliana and phylogenetic analysis of known cyclophilin proteins

We have isolated four members of the Arabidopsis cyclophilin (CyP) gene family, designated ROC1 to ROC4 (rotamase CyP). Deduced peptides of ROC1, 2 and 3 are 75% to 91% identical to Brassica napus cytosolic CyP, contain no leader peptides and include a conserved seven amino-acid insertion relative to mammalian cytosolic CyPs. Two other Arabidopsis CyPs, ROC5 (43H1; ATCYP1) and ROC6 (ATCYP2), share these features. ROC1, ROC2, ROC3 and ROC5 are expressed in all tested organs of light-grown plants. ROC2 and ROC5 show elevated expression in flowers. Expression of ROC1, ROC2, and ROC3 decreases in darkness and these genes also exhibit small elevations in expression upon wouding. The five Arabidopsis genes encoding putative cytosolic CyPs (ROC1, 2, 3, 5 and 6) contain no introns. In contrast, ROC4, which encodes a chloroplast stromal CyP, is interrupted by six introns. ROC4 is not expressed in roots, and is strongly induced by light. Phylogenetic trees of all known CyPs and CyP-related proteins provide evidence of possible horizontal transfer of CyP genes between prokaryotes and eukaryotes and of a possible polyphyletic origin of these proteins within eukaryotes. These trees also show significant grouping of eukaryotic CyPs on the basis of subcellular localization and structure. Mitochondrial CyPs are closely related to cytosolic CyPs of the source organism, but endoplasmic reticulum CyPs form separate clades. Known plant CyPs fall into three clades, one including the majority of higher-plant cytosolic CyPs, one including only ROC2 and a related rice CyP, and one including only chlorplast CyPs.
Estimation of Current Human Immunodeficiency Virus Incidence Rates from a Cross-Sectional Survey Using Early Diagnostic Tests

In sharp contrast to the considerable worldwide epidemiologic data available on acquired immunodeficiency syndrome incidence and human immunodeficiency virus (HIV) seroprevalence, there is relatively little information about current levels of HIV incidence rates. The authors suggest a novel approach for estimating current HIV incidence rates based on a single cross-sectional survey and on an epidemiologic model. The approach is based on diagnostic tests for HIV p24 antigen to identify individuals in the preantibody or window period (time between exposure to HIV and appearance of detectable HIV antibodies). Individuals in the preantibody period are likely to have been infected very recently because the duration of the preantibody period is relatively short. The authors report data on the duration of p24 antigenemia prior to HIV seroconversion. This duration together with the prevalence of p24 antigenemia obtained from a cross-sectional survey are used in an epidemiologic model to estimate current incidence rates. This approach of estimating incidence rates may be especially useful in developing countries and high-risk populations in which it is difficult to follow cohorts to identify seroconverters, and in the design of vaccine efficacy studies in which current incidence rates are crucial for calculating sample sizes.
A real-time qPCR assay to quantify Fusarium graminearum biomass in wheat kernels.

Aims: To develop a real-time PCR assay to quantify Fusarium graminearum biomass in blighted wheat kernels. Methods and Results: Primers designed to amplify a gene in the trichothecene biosynthetic cluster (TRI6) were evaluated for sensitivity and specificity. Primer pair Tri6_10F/Tri6_4R specifically and consistently amplified a 245-bp DNA fragment from F. graminearum. A workflow was developed and validated to extract DNA from infested grain. The assay detected as little as 10 μg of F. graminearum mycelia in 1 g of ground wheat grain with a high correlation between fungal biomass and cycle threshold values (R2 = 0·9912; P = 0·004). In field-inoculated grain, qPCR measurements of biomass correlated closely with deoxynivalenol levels (R = 0·82, P < 0·0001) and two visual techniques to assess grain quality (R = 0·88, P < 0·0001 and R = 0·81, P < 0·0001). Conclusions: The qPCR assay provided accurate and precise assessments of the amount of F. graminearum biomass in blighted wheat kernels. This method represents a technical advance over other approaches to quantify kernel colonization and real-time PCR detection methodologies for F. graminearum that do not correlate quantification of fungal genomic DNA to biomass. Significance and Impact of the Study: Quantifying F. graminearum biomass, especially low levels of growth associated with kernels that are visually asymptomatic, represents a new approach to screen for resistance to kernel infection, an understudied yet potentially important avenue to reduce the impact of head blight.
Semi-Automated Volumetric and Morphological Assessment of Glioblastoma Resection with Fluorescence-Guided Surgery

Glioblastoma (GBM) neurosurgical resection relies on contrast-enhanced MRI-based neuronavigation. However, it is well-known that infiltrating tumor extends beyond contrast enhancement. Fluorescence-guided surgery (FGS) using 5-aminolevulinic acid (5-ALA) was evaluated to improve extent of resection (EOR) of GBMs. Preoperative morphological tumor metrics were also assessed. Thirty patients from a phase II trial evaluating 5-ALA FGS in newly diagnosed GBM were assessed. Tumors were segmented preoperatively to assess morphological features as well as postoperatively to evaluate EOR and residual tumor volume (RTV). Median EOR and RTV were 94.3 % and 0.821 cm3, respectively. Preoperative surface area to volume ratio and RTV were significantly associated with overall survival, even when controlling for the known survival confounders. This study supports claims that 5-ALA FGS is helpful at decreasing tumor burden and prolonging survival in GBM. Moreover, morphological indices are shown to impact both resection and patient survival.
Molecular Basis of the Biological Function of Molybdenum MOLYBDENUM-FREE SULFITE OXIDASE FROM LIVERS OF TUNGSTEN-TREATED RATS

Abstract Livers of tungsten-treated rats have been shown to contain inactive protein which cross-reacts with antibody prepared against native rat liver sulfite oxidase. The cross-reacting material (CRM) was shown to be immunologically identical to the native enzyme by Ouchterlony double immunodiffusion. Difference spectrophotometry, acrylamide gel electrophoresis, and immunological analysis of the proteins of the mitochondrial intermembranous space from livers of control and tungsten-treated rats showed that, like native sulfite oxidase, the CRM was localized in this compartment. CRM was quantitated in terms of the amount of the b5-type heme of sulfite oxidase which was precipitable by the antibody and was shown to be present in amounts corresponding to almost 70% of control. Sulfite oxidase CRM was purified by the procedure established for native enzyme and shown to contain the b5 heme in stoichiometric amounts and no molybdenum. Tungsten was quantitated by a sensitive colorimetric technique and was found to be incorporated into 35% of the molybdenum-free molecules. Tungsten-containing sulfite oxidase was shown to have no detectable cytochrome c reductase activity. Tungsten in the enzyme could be visualized by EPR spectroscopy after reduction by dithionite. The signal at g = 1.87 was very similar in line shape to the g = 1.97 signal of molybdenum (V) in native sulfite oxidase. The native and inactive proteins were indistinguishable on acrylamide gels in the presence or absence of sodium dodecyl sulfate. The absorption spectra of the two proteins were quite similar in both the oxidized and reduced states, although the conditions required for reduction of the heme chromophore differed. The native enzyme was reduced by sulfite within 1 min; the inactive protein showed 30 to 40% reduction in the course of 30 min in the presence of sulfite, with full reduction achieved only upon the addition of dithionite. The difference spectrum of oxidized native sulfite oxidase minus inactive protein revealed subtle differences in the environments of the heme prosthetic group, hydrophobic aromatic residues, and possibly sulfhydrylmolybdenum linkages. Activity assays of the native enzyme complexed with antibody showed loss of ability to reduce O2 and cytochrome c but normal ferricyanide activity. EPR studies revealed that the molybdenum center of the enzyme in the complex was rapidly reducible by sulfite and maintained its sensitivity to anionic and pH effects. Sulfite oxidase in other rat tissues was shown to be antigenically similar to the liver enzyme.
How intangible factors contribute to economic development: Lessons from a mature local economy

Abstract Building on a case study of a mature manufacturing region in Massachusetts, this paper provides new evidence on the importance of nontraditional cost factors in determining regional growth. Specialized mature manufacturing firms that have broken the product cycle are identified. We then discuss development strategies for using “intangible” factors to promote such firms.
Phospholipid Substrate Specificity of Purified Human Plasma Lecithin: Cholesterol Acyltransferase

The reactivity of purified lecithin: cholesterol acyltransferase with a series of phospholipid substrates, in the presence and absence of the specific cofactor apo Al from human high density lipoprotein, indicated that the enzyme was specific for substrates containing a basic nitrogen atom, and that reaction was increased by N-methylation. Cholesteryl ester production from all substrates was stimulated by apo Al. This cofactor may act by trapping the cholesteryl ester product of the reaction.
The Mitochondrial Copper Metallochaperone Cox17 Exists as an Oligomeric, Polycopper Complex†

Cox17 is the candidate copper metallochaperone for delivery of copper ions to the mitochondrion for assembly of cytochrome c oxidase. Cox17 purified as a recombinant molecule lacking any purificati...
Effect of ion implantation on subsequent erosion and wear behavior of solids

The removal of material from a solid surface by mechanical forces is influenced by material properties (hardness, fracture toughness, yield strength, surface free energy) as well as system parameters (force, velocity of loading, environment). Ion implantation can modify many of the material properties either by directly affecting the deformation characteristics or indirectly by affecting the chemical or phase composition at the surface. The various forms of wear and erosion are analyzed to determine the material and system parameters which control material removal. The effects of implantation on these critical parameters are noted and examples of changes in surface topography under various test conditions are discussed.
The effect of a computer-assisted insulin protocol on glycemic control in a surgical intensive care unit.

Abstract Background: Computer-assisted insulin protocols (CAIPs) contain complex mathematical algorithms to assist with insulin dosing. This study compared the quality of glucose control utilizing a CAIP with a paper-based insulin protocol (PBIP). Methods: This before–after study identified consecutive patients who received continuous insulin therapy for at least 24 h. Patients were stratified into two groups (PBIP and CAIP). The target blood glucose range for both was 80–110 mg/dL. Hypoglycemia was defined as the percentage of patients with any glucose value <40 mg/dL. Variability was measured by reporting the SD for each patients mean glucose value. Results: There were 192 patients evaluated (PBIP, n = 145; CAIP, n = 47). More glucose readings were within target range using the CAIP protocol (49 ± 14% vs. 40 ± 12%, P < 0.001), but no difference in mean glucose was noted (113 ± 11 mg/dL with CAIP vs. 116 ± 11 mg/dL with PBIP, P = 0.067). The incidence of hypoglycemia was similar between the CAIP and PBIP...
Microfluidic self-assembly of tumor spheroids for anticancer drug discovery.

Creating multicellular tumor spheroids is critical for characterizing anticancer treatments since it may provide a better model than monolayer culture of in vivo tumors. Moreover, continuous dynamic perfusion allows the establishment of physiologically relevant drug profiles to exposed spheroids. Here we present a physiologically inspired design allowing microfluidic self-assembly of spheroids, formation of uniform spheroid arrays, and characterizations of spheroid dynamics all in one platform. Our microfluidic device is based on hydrodynamic trapping of cancer cells in controlled geometries and the formation of spheroids is enhanced by maintaining compact groups of the trapped cells due to continuous perfusion. It was found that spheroid formation speed (average of 7 h) and size uniformity increased with increased flow rate (up to 10 μl min−1). A large amount of tumor spheroids (7,500 spheroids per square centimeter) with a narrow size distribution (10 ± 1 cells per spheroid) can be formed in the device to provide a good platform for anticancer drug assays.
The Dielectric Circuit

The dielectric circuit is a baffling enigma to many undergraduate students of electrical engineering; indeed, to many engineers whose work is not intimately concerned with it. This outline of some of the elementary notions regarding electrostatics and the dielectric circuit is presented here because of its possible interest and value to students and others wishing to review the subject with the aim of attaining a working knowledge of it.