cssi/SciSciGPT-SciSciNet huggingface dataset:
The kyphoscoliotic type of Ehlers–Danlos syndrome (type VI): differential effects on the hydroxylation of lysine in collagens I and II revealed by analysis of cross-linked telopeptides from urine

The kyphoscoliotic type of Ehlers-Danlos syndrome (EDS type VIA) (OMIM 225400) is an autosomal recessive connective tissue disorder that results from mutations in the lysyl hydroxylase 1 gene (PLOD1) causing underhydroxylation of lysine residues in tissue collagens, particularly of skin. Previous studies have shown that the pool of collagen cross-linking amino acids, hydroxylysyl pyridinoline (HP) and lysyl pyridinoline (LP) excreted in urine has an abnormally low HP/LP ratio, which is diagnostic of the condition. Here we isolated cross-linked peptides containing these residues from the urine of a child with EDS VIA homozygous for a mutation that results in a stop codon and effective null expression of PLOD1 enzyme activity. Peptides that had originated from bone type I collagen and cartilage type II collagen were identified. A cross-linked N-telopeptide fraction that is derived from bone type I collagen contained only LP, no HP, which means that the helical lysines at residues 930 of alpha 1(I) and 933 of alpha 2(I) of the collagen triple-helix had not been hydroxylated. The equivalent peptide fraction from a normal child's urine gave a ratio of HP to LP of 1.5:1 typical for normal bone collagen. A second cross-linked peptide that is derived from the C-telopeptide domain of cartilage type II collagen showed both HP and LP in a 2:1 ratio, compared with 18:1 for the equivalent peptide from a normal child's urine. The results show that in EDS VIA, bone type I collagen is more markedly underhydroxylated than cartilage type II collagen, at least at those helical sites that form cross-links. The residual fraction of HP found in the urine of EDS VI patients therefore appears to be contributed in significant part by the degradation products of cartilage. Since PLOD1 is null, other PLOD genes must be responsible for the helical hydroxylation activity that results in HP. The presented approach of analyzing urinary cross-linked C-telopeptide fragments of type II collagen may allow the detection of chondrodysplasias due to genetic defects in lysyl hydroxylase isoforms active in cartilage.
Petrologic Changes in Fluvial Sediments in the Rio Nautla Drainage Basin, Veracruz, Mexico

Textural and compositional changes in fluvial sediments in the 3400 km 2 Rio Nautla drainage basin are discussed. Many different fluvial environments and rock types are present in this basin. The stream profiles are divided into three segments based on gradient. The headwaters segment is the steepest and contains high energy streams, while the intermediate segment has braided streams and the coastal segment consists of low-energy meandering streams. Sharp topographic breaks are present at the boundaries between the segments. Sediments found upstream from the coastal segment are bimodal mixtures of sand and gravel with metal grain sizes in the gravel range. They are poorly sorted, and are mostly positively skewed and leptokurtic. Skewhess and kurtosis indicate the proportions in which the sand and gravel are mixed in biomodal sediments and can be used to indicate the rate in which competence decreases after floodstage. Variation in grain size in the upper Rio Nautla drainage basin are determined by variations in the amount and size of gravels. In the coastal segment, unimodal, moderately well-sorted fine-to medium-grained sand is present. All of the gravel is deposited upstream from the coastal plain, and therefore never reaches the coastal plain. The composition of the Rio Nautla sediments reflects the dominance of volcanic rocks in the source area. Volcanic rock fragments, plagioclase, magnetite and pyroxenes are the most common constituents, but quartz, orthoclase and limestone are common and can even dominate the suite close to granitic and limestone outcrops. Sudden changes in composition are found in the headwaters segment, but not in the other segments which represent an integration of all lithologies found in the drainage basin. The area can best be compared to an alluvial fan, where gravel grades into non-marine sand and then into marine sand, silt and clay. The location of the inner margin of the coastal plain, where the last of the gravel settles out, may indicate the relative position of land and sea. If the land subsides or sealevel rises, the sand-gravel boundary moves inland. If sealevel is lowered or the land is uplifted, the boundary will move seaward.
Insufficient Emotion: Soul-searching by a Former Indicter of Strong Emotions:

Contrary to the many accounts of the destructive effects of strong emotions, this article argues that the most serious problems facing the world are caused by a deficiency rather than an excess of emotions. It then shows how an evolutionary account of emotion can explain when and why such deficiencies occur.
Regeneration of rat sciatic nerves in silicone tubes: characterization of the response to low intensity d.c. stimulation.

Abstract Endogenous d.c. electric fields have been postulated to play a role in normal development and repair functions of a variety of living systems. The corollary hypothesis, that exogenous electric fields can alter development and repair mechanisms, has led to the use of d.c. electric fields as a means to enhance mammalian peripheral nerve regeneration. This study investigates the response of transected rat sciatic nerves within silicone tubes to low intensity d.c. stimulation. In 40 rats, the right sciatic nerves were transected and sutured into silicone tubes, leaving a 5.0 mm gap between the stumps. The nerves were either treated with 10 μA d.c., with the cathode at the midpoint of the tube and the anode distant, or received no exogenous current. Three weeks later, transverse sections from the center of the tissue bridging the two segments were analysed by sampling approximately 12% of the cross sectional area, using × 1000 magnification on the light microscope. All non-stimulated (control) nerves showed regeneration of myelinated axons at the center of the bridge, while only 35% of the nerves stimulated with 10 μA had such a response. Of the nerves with regeneration of myelinated axons at the center of the tube, the control nerves had significantly more myelinated axons ( P = 0.0028) than treated nerves. Stimulated nerves showed bizarre regeneration responses, including formation of multiloculated cysts and neuroma-like formations. In control nerves there was a gradual tapering of axon number from proximal to distal in the regeneration bridge, while in the stimulated nerves there was a sharp decrease in the number of axons proximal to the cathode. We hypothesize that this effect is due to the accumulation of electrolysis products at the cathode, which inhibit regeneration through this region. Regeneration of transected rat sciatic nerves is not enhanced by electric currents applied in this manner. Previous work interpreted the increased number of axonal cross-sections in the tube as an increase in the absolute number of regenerating fibers. Our data suggest that the increased number of axonal cross-sections is due to neuroma formation, probably in response to the accumulation of electrolysis products at the cathode. This work brings into question claims of an enhancement of peripheral nerve regeneration by applied electric fields.
IPM: Challenges for the future

Abstract The forests of the world cover over three thousand million hectares. This represents roughly 23% of the total land area of the Earth, and equals almost one ha per head of population. To accommodate a projected world population of 6.4 million persons by the year 2000 — with its accompanying demands for food and fiber, effects on the land and its productivity, and on the environment — will present an exciting, difficult, and continuing challenge to resource managers. Research, academic, and resource management professionals face the particularly different challenge of analyzing and anticipating long-term research, technology, and educational needs to design programs to train professionals and to develop and effectively implement technology capable of meeting these changing resource and pest-management demands. Our future goals and actions in management, protection, and use of the Earth's natural resources must be approached with consideration of global conditions. As communication and transportation networks place us in closer contact with our global neighbors, it becomes increasingly clear that our resource management decisions, today and in the future, will not only affect our own future generations, but also those of our neighbors around the world.
A method for determining the number of documents needed for a gold standard corpus

Graphical abstractDisplay Omitted Highlights? Annotated documents are necessary for NLP machine learning, modeling and testing. ? We create a method to determine a required sample size for the annotation set. ? The probability of word capture from a corpus provides the basis for the method. ? Dictation letters from a pain management medical practice are used as an example. ? We also demonstrate steps for creating a representative sample of dictations. The unstructured narratives in medicine have been increasingly targeted for content extraction using the techniques of natural language processing (NLP). In most cases, these efforts are facilitated by creating a manually annotated set of narratives containing the ground truth; commonly referred to as a gold standard corpus. This corpus is used for modeling, fine-tuning, and testing NLP software as well as providing the basis for training in machine learning. Determining the number of annotated documents (size) for this corpus is important, but rarely described; rather, the factors of cost and time appear to dominate decision-making about corpus size. In this report, a method is outlined to determine gold standard size based on the capture probabilities for the unique words within a target corpus. To demonstrate this method, a corpus of dictation letters from the Michigan Pain Consultant (MPC) clinics for pain management are described and analyzed. A well-formed working corpus of 10,000 dictations was first constructed to provide a representative subset of the total, with no more than one dictation letter per patient. Each dictation was divided into words and common words were removed. The Poisson function was used to determine probabilities of word capture within samples taken from the working corpus, and then integrated over word length to give a single capture probability as a function of sample size. For these MPC dictations, a sample size of 500 documents is predicted to give a capture probability of approximately 0.95. Continuing the demonstration of sample selection, a provisional gold standard corpus of 500 documents was selected and examined for its similarity to the MPC structured coding and demographic data available for each patient. It is shown that a representative sample, of justifiable size, can be selected for use as a gold standard.
Induction of translocations by cyclophosphamide in different germ cell stages of male mice: cytological characterization and transmission.

Abstract Cytological and fertility tests were performed in F1 male mice derived from different germ-cell stages of male parents treated with cyclophosphamide (350 mg/kg body weight). The objectives of the present experiment were: (1) to determine the sensitivity of the male germ-cell stages to the induction of translocations by the compound, and (2) to characterize translocation configurations in F1 and F2 males, in order to obtain information about the pattern of chromosome breakage induced and its transmission to subsequent generations. Of 508 F1 males studied, 39 were partially sterile and 9 were fully sterile. The group of males conceived 8–21 days after treatment contained by far the highest proportion of partially sterile animals (30%). It was also the only group in which totally sterile animals (11%) were found. Of 25 semisterile males from this group, 24 gave evidence of translocations when spermatocytes were scored at diakinesis. The translocation frequencies in F1 derived from treated spermatozoa and spermatocytes were 14 and 1%, respectively. No translocations were detected cytologically 6 semisterile males derived from treated spermatogonial stages. These results indicate that spermatid stages are especially sensitive to the mutagenic action of cyclophosphamide. In 21 of the 31 semisterile translocation males (68%), the majority of the spermatocytes contained 18 bivalents plus a ring-of-four configuration, indicating that both breakpoints were relatively centrally located; and in several of these males, the frequency of cells with rings was close to 100%. In another 9 F1 males (29%) the predominant multivalent configuration was a chain-of-four, indicating one of the breakpoints to be relatively more terminally located; and in one male (3%), the majority of cells had two unequal bivalents, indicating both breakpoints to be fairly close to the ends of the chromosomes involved. Determination of centromere positions by the use of C-banding showed that chain-of-four configurations in any one male were predominantly of a given type. Associations of more than one translocation were observed in 11 of 31 translocation males, but in a very low frequency (about 1% of the spermatocytes). The results indicate that cyclophosphamide induces a relatively random pattern of chromosome break location. In this respect this mutagen more closely resembles X-rays than it does certain chemicals for which there isf evidence that breakpoint position is frequently subterminal. Our data indicate that the pattern of configurations observed in F1 was in general transmitted to F2.
The Effect of Anti-TNF-α Therapy on Spinal Bone Mineral Density in Patients with Crohn's Disease

Proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha) might be, at least partially, responsible for the development of osteopenia or osteoporosis in Crohn's disease. We investigated whether anti-TNF therapy for Crohn's disease could have any skeletal impact. Therefore, we studied the effects of infliximab, a monoclonal antibody against TNF-alpha with and without bisphosphonates, on spinal bone mineral density (BMD). The effect of corticosteroids was also analyzed. A retrospective cohort analysis was performed on 61 patients with Crohn's disease and low BMD by serial DXA scans. Twenty-three patients were on infliximab and 36 patients were on bisphosphonates. Mean duration between DXA scans was 2.2 +/- 0.99 years. After controlling for corticosteroid use, patients with concurrent infliximab and bisphosphonate treatment exhibited a greater increase in BMD compared to those on bisphosphonates alone (+6.7%/year vs. +4.46%/year, P= 0.045); corticosteroids inhibited this effect (P= 0.025). However, infliximab alone had no effects on BMD. Patients receiving bisphosphonates showed a significant increase in lumbar spine BMD compared to those not on bisphosphonates (+3.97% change in T score/year vs. -3.68%/year, P < 0.0001). Concurrent corticosteroid use significantly inhibited this effect (+2.15%/year vs. +4.97%/year, P= 0.0014). Concurrent infliximab use may confer an additional benefit to that already documented for bisphosphonate use alone; bisphosphonates are beneficial in the treatment of low BMD in patients with Crohn's disease, though corticosteroids may partially inhibit this effect.
High-repetition rate, narrow linewidth, and spatially controlled operation of a Q-switched Nd:YVO4 laser

We present a Nd:YVO 4 Q-switched oscillator with spectrally controlled output operating at repetition rates up to 25 kHz and providing energy up to 1.5 mJ in 50 ns pulses. Spectral control is provided by an intra-cavity volume Bragg grating (VBG), which locks the output wavelength to 1064.24 nm and narrows the spectral linewidth to less than 10 pm. The side-pumped geometry of the gain medium allows for controlled spatial profile and compactness (30x60 cm 2 ) of the total setup.
Acetylcholinesterase stain intensity variation in the rat dentate gyrus: a quantitative description based on digital image analysis

Three-dimensional patterns of variation in the intensity of acetylcholinesterase histochemical staining and the width of stain-defined subregions were quantified for the dentate gyrus of the adult male Long-Evans rat. Matched tissue sections sampled through the central hippocampal formation of five rats were measured with a digital image analysis computer system. The width and stain intensity were determined for defined portions of the dentate gyrus related to gross acetylcholinesterase staining patterns and the known distribution of dentate afferents. Normalized values reflecting stain intensity at defined positions within this standardized sampling array were examined to investigate regional differences in acetylcholinesterase distribution along the primary dendritic axis of dentate granule neurons. The data illustrate quantitative differences in the partitioning of acetylcholinesterase as a function of intrahippocampal position. The variation is more pronounced in the septal-temporal axis than the granule cell layer crest-tip axis. Furthermore, the septal-temporal variations in acetylcholinesterase intensity demonstrate some independence according to proximal-distal location within the molecular layer. The results suggest that acetylcholinesterase distribution within the dentate gyrus may reflect local physiological characteristics of those afferent systems related to this enzyme, including but not necessarily limited to those that are specifically cholinergic.
Cover Picture: Recent Advances in the Chemistry of Metallacarboranes (Eur. J. Inorg. Chem. 22/2003)

The cover picture shows a typical bent-sandwich commo-metallacorborane product as well as its starting nido-ycarborane precursor of the smaller carborane cage system, together in a novel cluster. Details are discussed in the Microreview by N. S. Hosmane and J. A. Maguire on p. 3989 ff. The authors are indebted to their many students and co-workers who have borne the brunt of doing, and to the National Science Foundation, Alexander von Humboldt-Stiftung (to N. S. H.) and the R. A. Welch Foundation (to J. A. M.) for their generous support.
Selection of systems analysts and programmer trainees

The subject of this talk is primarily the selection of Systems Analysts. Time permitting, I shall also discuss work done on the selection of programmer trainees. The research program, as many of you have heard described in previous talks, was divided into three phases. The first was the job analysis phase in which 17 job dimensions were revealed to cover systems analyst and programmer positions. The second phase dealt with the development of criterion tests for evaluating programmer and systems analyst performance. The third phase was concerned with the selection of people for training in programming and systems analysis. I have reported on the results of the job analysis phase, and on the development and use of a test dealing with programmer proficiency, the Basic Programming Knowledge Test. Today I will report on the other criterion test, the Systems Analysis Test. A detailed report on the development of the Systems Analysis Test and an analysis of the results of its use is planned. I will discuss some of those results here.
The Development of Competencies for Specialists in Dental Public Health

This paper describes the process of developing new competency statements and performance indicators for the specialty of dental public health. These competencies help define the specialty and provide a base for educational curricula and the specialty board examination. The process included a survey of four target groups: all board members, all directors or co-directors of advanced education programs in dental public health, people who had become diplomates in the last three years, and all students currently enrolled in dental public health programs. Many constituencies were represented at the workshop, conducted in May 1997, to develop the competency document. After the workshop, the document underwent a series of review activities.
Roots and Shoots of Management Thought

Management theory and practice are not created in a vacuum nor are they created at the whim of management writers. Contemporary management theory and practice are rooted in the most influential thoughts and values dominant in philosophy and science of about a century ago. Management thoughts that will blossom at the turn of the twenty‐first century are now only tender shoots which are shyly nudging through their stem of current concepts. To anticipate the future bends, turns and shapes of the surviving shoots, we must look at their philosophic and scientific roots and predict the nature of the environment that will nurture their growth during the next two decades. Basic philosophical positions are disseminated into a society through artists, writers and educators who interpret these positions within their individual fields. As new ways of thinking become dominant in a culture, managers must find ways of behaving that are compatible with them. A nineteenth century manager would be totally incapable of contending with the ways of thinking of employees today. Workers who reject traditional principles, values and authority practices will not respond well to the manager who assumes them to be inviolable.
Selective Alterations of Transcription Factors in MPP+-Induced Neurotoxicity in PC12 Cells

Abstract MPP+ (1-methyl-4-phenylpyridinium; the active metabolite of the neurotoxin MPTP (1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine)) depletes dopamine (DA) content and elicits cell death in PC12 cells. However, the mechanism of MPP+-induced neurotoxicity is still unclear. In this study, the dose response and time-course of MPP+-induced DA depletion and decreased cell viability were determined in nerve growth factor (NGF)-differentiated PC12 cells. The alteration of transcription factors (TFs) induced by MPP+ from a selected dose level and time point was then evaluated using protein/DNA-binding arrays. K-means clustering analysis identified four patterns of protein/DNA-binding changes. Three of the 28 TFs identified in PC12 cells increased by 100% (p53, PRE, Smad SBE) and 2 decreased by 50% (HSE, RXR(DR1)) of control with MPP+ treatment. In addition, three TFs decreased within the range of 33–50% (TFIID, E2F1, CREB) and two TFs increased within the range of 50–100% (PAX-5, Stat4). An electrophoretic mobility shift assay (EMSA) was used to confirm the changes of p53 and HSE. The observed changes in TFs correlated with the alterations of DA and cell viability. The data indicates that selective transcription factors are involved in MPP+-induced neurotoxicity and it provides mechanistic information that may be applicable to animal studies with MPTP and clinical studies of Parkinson's disease.
The HCO B̃2A′ ↔ X̃2A′ System: Fluorescence Excitation and Stimulated Emission Pumping Spectra

Abstract The 000 band of~ the HCO B2A′ ↔ X2A′ system, observed at 0.06 cm−1 resolution in a ∼300 K fluorescence excitation spectrum, is rotationally analyzed. The principal molecular constants (in cm−1, 1σ uncertainties in parentheses), derived from a fit to K′a = 0 and 1 levels only, are in cm−1: [formula] Rotational congestion combined with irregularity of the K′a, K′a + 1 intervals, presented definitive assignments for K′a > 2 levels. A vibronic level at T0 = 41 284 cm−1, previously assigned as the zero-point level of a "C2A″" electronic state, is conclusively shown by its hybrid a, b-type rotational contour to be the B2A′ (1, 0, 0) level. From the relative intensities of a-type and b-type rotational transitions, the B2A′ - X2A′ 000 band electric dipole transition moment is found to lie (in the plane of the HCO molecule) at an angle of 31 (4)° relative to the a-inertial axis. Stimulated emission pumping (SEP) spectra (0.06 cm−1 resolution) of two X2A′-state vibrational "resonances," (vCH, vCO, vBEND) = (0, 5, 0) and (0, 4, 1) located at Tv = 9091.97 (3)and 8478 (1) cm−1, respectively, both lying well above thc H-CO dissociation limit, exhibited typical asymmetric top rotational structure and highly vibrational mode specific linewidths: Γ(0,5,0) ≍ 0.7 cm−1 (broadened by unresolved spin-rotation splittings) and Γ(0,4,1) ≍ 2.1 cm−1. Despite the lower energy of the (0, 4, 1) level, its much larger linewidth than that of (0, 5, 0) implies that the bending vibration (ν″3) is much more effective than the CO stretch (ν″2) in promoting dissociation.
Renal expression of a transforming growth factor-α transgene accelerates the progression of inherited, slowly progressive polycystic kidney disease in the mouse

Polycystic kidney disease (PKD) is a prevalent inherited disease in human beings. The pathogenesis of PKD is as yet unclear. The epidermal growth factor family of proteins has been implicated in PKD based largely on in vitro data. To determine whether these growth factors contribute to the progression of inherited PKD in vivo, we crossed mice with a transgene for human transforming growth factor-α (TGF-α, a member of the epidermal growth factor (EGF) family) and mice with the pcy gene (which causes a slowly progressive form of PKD very similar to human autosomal dominant PKD). Renal expression of the TGF-α transgene in cystic mice (homozygous for the pcy gene) accelerated the development of PKD as shown by an increased kidney weight as a percent of body weight and an increased volume density of renal cysts at 8.5 weeks of age. However, renal expression of the TGF-α transgene did not appear to precociously initiate cyst development (at 6.5 weeks), nor did it cause an increase in the final degree of renal enlargement (at 29 weeks). Thus TGF-α accelerated the enlargement of cysts once initiated. At 8.5 weeks of age, renal expression of the TGF-α mRNA correlated positively with the amount of renal enlargement. At all time points studied, cystic kidneys exhibited increased expression of c-myc mRNA as compared with phenotypic normal kidneys, consistent with PKD being a hyperplastic disease of renal tubules. However, the renal expression of c-myc in 8.5 week cystic kidneys, with or without the transgene, did not correlate with the degree of renal enlargement. The results of this study suggest that EGF-like proteins may accelerate the progression of inherited renal cystic disease. However, the final degree of cystic change is dictated by the primary disease process rather than by the continued presence of growth factor.
Kant’s Emergence and Sellarsian Cognitive Science

The paper argues, against current views that see Kant as giving abstract descriptions of cognitive mechanisms (after the fashion of functionalism in cognitive science), that Kant sees mental phenomena as akin to emergent phenomena in a sense traditionally opposed to mechanism. After distinguishing several relevant notions of emergence, the paper distinguishes several of Kant’s basic emergentist theses, including his emergent materialism in chemistry and a species of mental emergence modelled on that chemical emergence. However, Kant’s doctrine of the epigenesis of pure Reason is argued to be Kant’s most fundamental emergentist thesis. The paper argues that Kant’s notion of mental emergence sheds light on some very puzzling aspects of his remarks about the unity of intuition and concept emphasized by Wilfrid Sellars. The paper sketches some of the problems in contemporary cognitive science and shows how a Sellarsian emergentism inspired by Kant addresses some of these problems and provides an interesting alternative to the kind of mechanistic positions that have tended to dominate the field. Finally, the paper locates the present emergentist reading with respect to the perspectivist reading of Kant.
Health Disparities in Later Life: A Simultaneous Equations Analysis of Utilization

Objective: This article examines health disparities between older Blacks/Whites by recognizing the importance of health services utilization. Although previous studies have examined health and utilization independently, this is among the first to (a) model its endogenous relation with utilization, and (b) use a continuous measure for health. Data: Household Component files from Medical Expenditures Panel Survey (MEPS) from 2004 and 2005, with 1,369 observations (1,169 for White and 200 for Black) between the ages of 61-69. Methods: The methods employed are two-equation modeling where Medicare eligibility functions as the identification criterion and also as an exogenous shock. Results: The results show older Blacks continue to remain in poorer health despite access to care and insurance status. The author shows underutilization accounts for some of this observed disparity and offers novel approaches to overcome this issue. Conclusion: With the baby-boom cohort approaching retirement, this area of research...
Central nervous system myelination in mice with deficient expression of Notch1 receptor

Activity of the Notch1 gene is known to inhibit oligodendrocyte (OL) differentiation in vitro. We tested the hypothesis that the Notch1 pathway regulates in vivo myelin formation, by examining brain myelination of Notch1 receptor null heterozygotes mutant animals (Notch1+/–). We show that a deficiency in Notch1 expression leads to increased abundance of products of specific myelin genes in myelinated areas of the brain during the first 2 weeks of postnatal life. We observed increased numbers of myelinated axons in optic nerves and the presence of myelinated fibers in the molecular layer (ML) of the Notch1+/– cerebella. These findings were accompanied by up-regulation of Mash1 and down-regulation of Hes5 proteins. In addition, we found expression of Jagged1, one of the Notch1 activators, in unmyelinated axons of the cerebellar ML during normal development. Our findings indicate that the Jagged/Notch signaling pathway might actively participate in the regulation of myelination during central nervous system development and suggest that certain neuronal populations might regulate whether their axons are myelinated by the expression of inhibitory signals such as Jagged1. © 2002 Wiley-Liss, Inc.
Applications of aqueous two-phase partition to isolation of membranes from plants: a periodic NADH oxidase activity as a marker for right side-out plasma membrane vesicles.

Phase separations using standardized mixtures of polyethylene glycol, dextran and potassium phosphate are used widely to prepare highly purified plasma membranes from plants and in the preparation of chloroplast subfractions. Other uses include the removal of right side-out plasma membrane vesicles as contaminants from Golgi apparatus, endoplasmic reticulum and tonoplast (vacuole membrane) fractions and separation of right side-out and inside-out plasma membrane vesicles. The higher degree of separation between plasma membranes into the upper phase and internal membranes into the lower phase is in large measure due to the fact that only plasma membranes are oriented cytoplasmic side in. Most other membranes are oriented cytoplasmic side-out. This property extends to separations of right side-out and inside-out plasma membrane vesicles and to the separation of right side-out and inside-out sub-mitochondrial particles. The inside-out vesicles partition into the lower phase whereas the right side-out vesicles remain in the upper phase. The lack of efficacy of aqueous two-phase partitioning in other types of membrane separations is apparently due to the fact that surface characteristics that may distinguish different internal membranes are not located at the cytosolic membrane surface. At present there are no direct enzymatic markers for right side-out plasma membrane vesicles from plants. Demonstrations of sidedness and estimates of fraction purity are based on measurements of latency of marker enzymes, e.g., ATPases, at the cytosolic surface. This report describes a periodic NADH oxidase as an enzyme marker for right side-out plasma membrane vesicles not requiring detergent disruptions of vesicles for measurement of activity.
Routine positron emission tomography does not alter nodal staging in patients undergoing EUS-guided FNA for esophageal cancer

Background Although EUS-guided FNA (EUS-FNA) and 18F-fluorodeoxyglucose–positron emission tomography (FDG-PET) are both used in the staging of esophageal cancer, the utility of routinely performing both tests is unclear. Objectives The primary aim of the study was to determine the benefit of routine FDG-PET for esophageal cancer nodal staging in patients undergoing EUS-FNA. The secondary objective was to determine EUS criteria that selectively identify patients in whom PET yields additional information. Design Retrospective chart review. Setting Tertiary-care academic medical center. Patients and Interventions All patients who underwent both EUS and PET for initial staging of esophageal cancer between April 2003 and August 2007. Main Outcome Measurements EUS and PET detection of malignant lymph nodes and distant metastases. Results Of 242 patients who underwent esophageal EUS for a malignant indication, 148 also underwent PET within 30 days. EUS detected locoregional-node disease by EUS criteria or cytology in 92 patients, and PET was positive in a minority of these patients (n = 41 [45%]). For celiac-node staging, PET was positive in 2 of 17 patients (12%) with celiac-node involvement detected by EUS. EUS was also significantly more sensitive than PET in the detection of nodal disease confirmed by cytology or histology (86% vs 44%). PET did not alter nodal staging in any patient with complete EUS-FNA. PET identified distant metastases only in those patients with incomplete EUS or nodal disease detected by EUS. Limitations Single institution, retrospective analysis. Conclusions The addition of PET to a complete EUS examination did not alter regional-node or celiac-node staging. PET performance in overall staging is strongly associated with EUS assessment of lymph nodes.
Cyclosporin a has low potency as a calcineurin inhibitor in cells expressing high levels of P-glycoprotein

Cyclosporin A (CsA) is a widely-used immunosuppressant drug whose therapeutic and toxic actions are mediated through inhibition of calcineurin (CN), a calcium- and calmodulin-dependent phosphatase. Inhibition of CN by CsA requires drug binding to its protein cofactor in the inhibition, cyclophilin. Because cyclophilin is a high affinity target for CsA it is expected that this protein can act as a reservoir for the drug in the cell and may be able to inhibit cellular efflux of CsA. P-glycoprotein (P-gp) is known to increase the rate of CsA efflux from CsA loaded cells but it is not clear if the P-gp drug efflux pump can compete effectively with cyclophilin at therapeutically relevant concentrations of CsA. To test the hypothesis that increased expression of P-gp confers protection against CsA-dependent inhibition of CN phosphatase activity, KB-V cells expressing varying levels of P-gp were analyzed to determine the potency of CsA as a CN inhibitor. When intact cells were treated with CsA, a positive correlation was observed between P-gp expression and resistance to CsA-dependent inhibition of CN: the IC50 is approximately 20-fold higher in the multidrug resistant epidermal carcinoma cell line, KB-V, which expresses P-gp at a high level than in the parental, KB, cell line expressing very low levels of P-gp. The resistance displayed by KB-V cells is abrogated by co-administration of the P-gp inhibitor verapamil, whereas verapamil has no effect on CsA potency in control KB cells. In cell lysates from KB-V cells with different amounts of P-gp CsA exhibits equivalent potency, indicating that the difference in sensitivity to CsA among the cell types requires maintenance of cell integrity. These observations support the view that resistance to CN inhibition by CsA occurs in cells with moderately elevated P-gp activity. Therefore, P-gp activity appears to be an important determinant of CsA cellular specificity for both therapeutic and toxic effects.
Drug abuse and neuropathogenesis of HIV infection: role of DC-SIGN and IDO

Abstract Dendritic cells are the critical mediators of various immune responses and are the first line of defense against any infection including HIV. They play a major role in harboring HIV and the subsequent infection of T cells and passage of virus through the blood–brain barrier (BBB). The recently discovered DC-specific, CD4-independent HIV attachment receptor, DC-SIGN, and T-cell suppressing factor, indolamine 2,3-dioxygenase (IDO), are known to play a critical role in the immuno-neuropathogenesis of HIV infection. Since brain microvascular cells (BMVEC) express dendritic cell (DC)-specific C type ICAM-3 grabbing nonintegrin (DC-SIGN), it is possible that DC-SIGN may play a critical role in human immunodeficiency virus-type 1 (HIV-1) infection and migration of infected DC across BBB. Matrix metalloproteinases (MMPs) are proteolytic enzymes known to be responsible for maintenance, turnover and integrity of extracellular matrix. Our results show that cocaine upregulates IDO and DC-SIGN expression by DC. Further, cocaine upregulates DC-SIGN and MMPs in BMVEC supporting the hypothesis that cocaine causes membrane permeability facilitating endothelial transmigration of infected DC in to the CNS. Targeting DC-SIGN and IDO with specific monoclonal antibodies, inexpensive synthetic antagonists, antisense oligonucleotides and siRNA may lead to develop novel treatment strategies particularly in high-risk populations such as cocaine users.
Direct fluorophore conjugation to genomic DNA for microarray-based epigenomic profiling

A methodology for microarray based epigenomic profiling is presented. The method relies on platinum-based fluorescence labeling reagents for direct (non-enzymatic) labeling of DNA and RNA. This is a work in progress and only preliminary data is presented here.
Treatment of Intercompany Transfer Pricing for Tax Purposes: A Survey of Legislative and Administrative Issues

Tax authorities in several countries have intensified their surveillance of intercompany transfer pricing in recent years. This paper examines the legislative and administrative issues related to the treatment of intercompany transfer pricing for tax purposes. It reviews the existing international guidelines and national rules on methods for determining appropriate transfer prices, as well as the issues related to tax administration practices for the implementation of those rules. Various systems, proposed or introduced to improve the predictability of taxation, are also examined. This paper further reviews the recent discussions on the “commensurate-with-income” standard and the pricing methodologies proposed thereunder. It finally reviews some alternative approaches to international income allocation which are proposed or adopted in lieu of the transfer pricing approach.
On the binding determinants of the glutamate agonist with the glutamate receptor ligand binding domain.

Ionotropic glutamate receptors (GluRs) are ligand-gated membrane channel proteins found in the central neural system that mediate a fast excitatory response of neurons. In this paper, we report theoretical analysis of the ligand-protein interactions in the binding pocket of the S1S2 (ligand binding) domain of the GluR2 receptor in the closed conformation. By utilizing several theoretical methods ranging from continuum electrostatics to all-atom molecular dynamics simulations and quantum chemical calculations, we were able to characterize in detail glutamate agonist binding to the wild-type and E705D mutant proteins. A theoretical model of the protein-ligand interactions is validated via direct comparison of theoretical and Fourier transform infrared spectroscopy (FTIR) measured frequency shifts of the ligand's carboxylate group vibrations (Jayaraman et al. (2000) Biochemistry 39, 8693-8697; Cheng et al. (2002) Biochemistry 41, 1602-1608). A detailed picture of the interactions in the binding site is inferred by analyzing contributions to vibrational frequencies produced by protein residues forming the ligand-binding pocket. The role of mobility and hydrogen-bonding network of water in the ligand-binding pocket and the contribution of protein residues exposed in the binding pocket to the binding and selectivity of the ligand are discussed. It is demonstrated that the molecular surface of the protein in the ligand-free state has mainly positive electrostatic potential attractive to the negatively charged ligand, and the potential produced by the protein in the ligand-binding pocket in the closed state is complementary to the distribution of the electrostatic potential produced by the ligand itself. Such charge complementarity ensures specificity to the unique charge distribution of the ligand.
Evaluation of an ATP photometer for measuring 14C activity

An evaluation was made of the suitability of an ATP photometer for field measurements of phytoplankton /sup 14/C activity. Over a wide range of /sup 14/C activity the light output recorded by the photometer was linear. The activity of a natural phytoplankton sample can be accurately determined with such an instrument; samples must be allowed to dark-adapt before analysis.
Atomic ordering in GaAs0.5Sb0.5 grown by molecular beam epitaxy

Abstract Ordered microstructures in GaAs 0.5 Sb 0.5 grown by molecular beam epitaxy have been studied by transmission electron microscopy. Observations of high resolution and dark field images, and diffuse scattering suggest the existence of plate-shaped microdomains of the ordered phase which are parallel to the growth plane and embedded by the matrix of the disordered phase. Intensity distributions of diffuse scattering have been calculated based on the model of plate-shaped microdomains. The calculations have correctly reproduced main features of observed diffuse scattering.
Substituted polyamides as precursors for alkyl and alkenyl polybenzoxazoles

Polymers with heteroaromatic repeat units have been known for many years to exhibit good thermal and oxidative stability. Polybenzimidazoles (1), polybenzothiazoles (2), and polybenzoxazoles (3,4) were first reported in the late ‘50’s and early ‘60’s and have since been under widespread investigation. Both AA-BB and AB monomer systems have been employed in the synthesis of high molecular weight polymers. (5) The thermal stability in nitrogen atmosphere of the completely aromatic AB polymers prepared from the various 3,4-disubstituted benzoic acids decreased in the order benzimidazoles>benzothiazole>benzoxazole. In air, however, all three types of polymers possessed similar stability.
Arthroscopically assisted combined anterior and posterior cruciate ligament reconstruction.

This article presents the minimum 2-year results (range, 24 to 48 months) of 20 arthroscopically assisted combined anterior cruciate ligament/posterior cruciate ligament (ACL/PCL) reconstructions, evaluated preoperatively and postoperatively using the Tegner, Lysholm, and Hospital for Special Surgery knee ligament rating scales, and the KT 1000 knee ligament arthrometer (Medmetric Corp, San Diego, CA). There were 16 men or boys, 4 women or girls; 9 right, 11 left; 10 acute, and 10 chronic knee injuries. Ligament injuries included 1 ACL/PCL tear, 2 ACL/PCL/medial collateral ligament (MCL)/posterior lateral corner tears. 7 ACL/PCL/MCL tears, and 10 ACL/PCL/posterior lateral corner tears. ACLs were reconstructed using autograft or allograft patellar tendons. PCLs were reconstructed using allograft Achilles tendon, or autograft patellar tendon. MCL tears were successfully treated with bracing. Posterior lateral instability was successfully treated with long head of the biceps femoris tendon tenodesis. Tegner, Lysholm, and Hospital for Special Surgery knee ligament rating scales significantly improved preoperatively to postoperatively (P = .0001). Corrected anterior KT 1000 measurements improved from preoperative to postoperative status (P = .0078).
The Link between Firm Financial Performance and Investment in Sustainability Initiatives

While sustainability initiatives by firms are increasingly encouraged by customers, investors, and the government, the economics of sustainable decisions remains in question. The study described in this paper examines the link between sustainability and economic performance for the hospitality industry, as compared with other businesses. Using data spanning 1991 through 2011 from MSCI’s Environmental, Social, and Governance (ESG) Indices and credit ratings from Standard and Poor’s representing 16,325 firm-years, the analysis finds that hospitality firms on average invest more in environmental programs than do businesses in other industries; that hospitality firms have significantly fewer environmental concerns; that strong financial performance leads to increased investments; and that going green, in turn, pays off in future periods, creating a virtuous cycle. One implication is that hospitality firms should go forward confidently in establishing their sustainability programs, as it appears that customers...
Roles, Quandaries, and Remedies: Teaching Professional Boundaries to Medical Students

This article conceptualizes a predictable set of tensions that medical students experience in their new roles with patients on clinical clerkships: empathy versus overidentification, objectivity ve...
Using Misuse Patterns for VoIP Steganalysis

The growing interest in Voice over Internet Protocol (VoIP) communications increased the fear that criminal and terrorist groups are switching to this technology to coordinate their operations. VoIP services that cannot be monitored and lawfully intercepted may be used to perform illegal activity. Converged networks are vulnerable to steganographic attacks due to their high bandwidth usage. This feature provides a way to embed hidden messages in either the VoIP signaling or media streams making steganalysis harder to accomplish. This paper discusses a systematic approach to analyze steganography in VoIP using misuse patterns [Pel09]. Misuse patterns describe, from the point of view of the attacker, how a type of information misuse is performed, analyzes the ways of stopping the attack, and considers how to trace the attack once it has happened. The pattern also attempts to correlate events with specific parts of the system. We will use these semiformal models as a method to improve the detection of embedded hidden messages in IP telephony.
Estrogen Replacement Therapy and Cognitive Functioning in the Atherosclerosis Risk in Communities (ARIC) Study

The association of estrogen replacement therapy (ERT) with cognitive functioning was assessed in 6,110 women aged 48-67 years participating in the Atherosclerosis Risk in Communities (ARIC) study, a multicenter longitudinal investigation. ERT was evaluated in relation to results of three cognitive tests (the Delayed Word Recall (DWR) Test, the Digit Symbol Subtest of the Wechsler Adult intelligence Scale-Revised (DSS/WAIS-R), and the Word Fluency (WF) Test) using data from the first follow-up visit of the cohort (1990-1992). No consistent associations were seen between ERT and either the DWR test or the DSS/WAIS-R after adjusting for age, education, and additional covariates previously found to be associated with cognitive function scores. Among surgically menopausal women aged 48-57 years, adjusted mean WF scores were slightly greater in ERT current users (mean WF 35.9) than in never users (mean WF 33.5) (p < 0.02); and within current users, adjusted WF scores increased with duration of ERT use. However, the finding that ERT was associated with a slightly higher level of performance on only one of three measures offers little support for the hypothesis that ERT has a major protective effect on cognitive function in women less than 68 years of age. The generalizability of these findings to older women who are more likely to experience cognitive decline and who may be using ERT for longer periods of time is limited by the relatively young age of the cohort.