cssi/SciSciGPT-SciSciNet huggingface dataset:
MEK Inhibitor-Associated Central Retinal Vein Occlusion Associated with Hyperhomocysteinemia and MTHFR Variants.

Background Central retinal vein occlusion (CRVO) is a visually threatening event that has rarely been observed in patients taking MEK1/2 inhibitors and that may necessitate permanent discontinuation of a potentially efficacious therapy. We investigated the clinical characteristics of CRVO in patients on mitogen-activated protein kinase kinase (MEK) inhibition to better understand their predisposing factors and clinical course. Case series This was a single-center, retrospective cohort study (between December 2006 and September 2018). Three of 546 patients enrolled in 46 prospective trials involving treatment with MEK inhibitors at Memorial Sloan Kettering Cancer Center were identified as having CRVO. Clinical examination and course, multimodal ophthalmic imaging, and serum laboratory results (including homocysteine levels and genetic variants of methylene tetrahydrofolate reductase [MTHFR]) were reviewed for the 3 affected patients. All 3 patients with MEK inhibitor-associated CRVO had elevated serum homocysteine and gene variants of MTHFR (1 homozygous for A1298C, 1 heterozygous for A1298C, and 1 homozygous for C677T). Following intravitreous injections of anti-VEGF and discontinuation of drug, all patients regained vision to their baseline. Discussion MEK inhibitor-associated CRVO is a rare event which can exhibit visual recovery after drug cessation and intravitreous anti-VEGF injections. In this cohort, it was associated with hyperhomocysteinemia and genetic mutations in MTHFR, suggesting a potential role for hyperhomocysteinemia screening prior to initiation of MEK inhibitor therapy.
Priests in the Temple of Justice: The Indian Legal Complex and the Basic Structure Doctrine

This chapter explores the critical role played by the Indian legal complex in the battles over protection of property rights, fundamental rights, constitutionalism, and the rule of law in the Indian Supreme Court. In these battles, the Indian legal complex played an important role in developing the legal and doctrinal arguments that were ultimately adopted by the Court in a series of landmark decisions asserting and developing the basic structure doctrine. The push to advance the basic structure doctrine in India was characterized by initial contestation between leading lawyers and political leaders in the ruling Congress Party, and conservative lawyers and political leaders from conservative opposition parties over land reform policies and protections for property rights. The chapter traces the role of government lawyers, legal academia and the private bar, in the battle over the basic structure doctrine, examining how subset of the legal complex helped advance and build support for the “basic structure” doctrine, and concludes by analyzing the legal and political battles over the basic structure doctrine within India from the larger perspective of the legal complex, and its broader implications for political liberalism in India.
The SmI2/TEU--Mediated Cyclization of Unsaturated Halides.

The combination of SmI2 and the conjugate base of triethylurea (TEU–) has been shown to favor the cyclization of unsaturated halides over direct reduction to a much greater extent than other SmI2-b...
Hexokinase-2 is a key therapeutic target in brain metastasis derived from breast cancer.

4354 The prevalence of brain metastasis from breast cancer is increasing. Current treatment options are limited and have no impact on survival. We are evaluating several potential therapeutic targets identified from cDNA microarray analysis of surgically resected human brain metastases. One of these, hexokinase II (HK-2), was validated using quantitative RT-PCR, and showed an approximately 2-fold up-regulation (p=0.01) in brain metastases (n=8) compared to unmatched primary invasive ductal breast carcinomas (n=8). Since HK-2 is not normally found in brain, this suggests that this isoenzyme may be a selective target for metastatic disease in this organ. HK-2 is up-regulated in many tumors, and belongs to a family of four hexokinases which play a vital role in the generation of ATP as they catalyze the first step of the glycolytic pathway converting glucose to glucose-6-phosphate. Production of this substrate also drives the pentose phosphate pathway providing many components required for cell growth. In addition, through mitochondrial binding, HK-2 inhibits apoptosis. We therefore hypothesized that HK-2 would play a key role in cell growth and survival in brain metastasis derived from breast cancer, and that its level of expression would affect overall survival. To test this hypothesis we examined survival curves in patients that were divided into one of two groups based on the degree of HK-2 expression in brain metastases, as determined by immunohistochemistry. Median survival for patients (n=94) with a high level of HK-2 was 9.6 months post-surgery as compared to a median survival of 17.5 months in patients (n=19) with a low level of HK-2 (p=0.0275 by two-tailed log rank test). To further validate HK-2 as a therapeutic target and evaluate the functional role of HK-2 in brain metastases, we are using a human breast cancer cell subline that is selectively metastatic to the brain (MDA-MB-231BR). These cells were transduced using VSV-g pseudotyped lentiviral particles carrying a shRNA targeting either HK-2 or a non-target control (Sigma-Aldrich). Knockdown of HK-2 was verified by Western blotting and QT-PCR. Cell growth is measured using 5-bromo-29-deoxy-uridine labeling. Knockdown of HK-2 expression by 95 % inhibited tumor cell proliferation by 40 % (p=0.0012 by two-tailed t test) under normal growth conditions at five days. These data suggest that over-expression of HK-2 is associated with poorer overall patient survival because it plays a key role in the proliferation and long-term survival of metastatic cells in brain. Thus, HK-2 is likely an important therapeutic targetin brain metastasis derived from breast cancer.
Processing pronouns in global discourse context

This study examined the interpretation and processing of third-person pronouns when global discourse context supports a less-salient referent as antecedent of a subject pronoun. In particular, we investigated whether such information cancels a default generalized conversational implicature (GCI) biasing a local subject antecedent interpretation for an English overt pronoun. Eye-tracking data was recorded as participants heard four-sentence mini-stories with one of three Contexts: one biasing the subject of the previous clause as antecedent (SB), one biasing another human referent (OB), and one neutral to biasing either referent. Results showed that looking patterns did not diverge in OB and Neutral conditions until after crucial information tying into the larger discourse context was given in the post-pronoun verb. Strong preferences for non-subject referents did not emerge until after the sentence ended, a time-course consistent with participants calculating and then cancelling a default implicature for a subject antecedent. Meanwhile, discourse context reinforcing the default subject implicature in the SB condition facilitated processing, in terms of less time spent looking at either human referent compared the Neutral condition. Overall, results suggest that upon hearing an overt pronoun, English speakers first calculate a GCI that results in a local subject antecedent interpretation, but that, like all implicatures, this GCI can be defeated by contextual factors.
Expertise Matters: Privacy Perceptions and Practices in Response to Behavioral Targeting

This paper provides psychological explanations of young adults’ privacy attitude and behavior based on their computer expertise. Interviews with 22 young adults with varying levels of computer expertise showed that their self-efficacy regarding privacy and security threats largely differed from their knowledge and that their behavior was more aligned with their knowledge than self-efficacy. Consistent with the Elaboration Likelihood Model (Petty & Cacioppo, 1984), users were relying on peripheral cues to process information related to security due to their lack of knowledge.
Pharmacist Allowances for the Dispensing of Emergency or Continuation of Therapy Prescription Refills and the COVID-19 Impact: A Multistate Legal Review

The COVID-19 pandemic has taught Americans many lessons, including what can happen when our healthcare system is strained. During the pandemic, certain healthcare related activities such as seeing or contacting a practitioner to receive a prescription refill may have been a challenge for some patients that could have interfered in the patient’s medication adherence and continuity of care. Given these circumstances, the pandemic also shed light on the necessity for pharmacists to dispense emergency refills, which often is based on variable state pharmacy laws and regulations. State pharmacy laws and regulations vary from allowing pharmacists to dispense as much medication that is required for the patient to receive a new prescription to emergency refills being allowed only in the direst situations to save a patient’s life. State pharmacy laws and regulations vary in the allowable quantities that may be dispensed, the federal schedule of controlled substance medications, and the circumstances they can be dispensed. In many cases, COVID-19 emergency regulations, governor executive orders and board of pharmacy guidance have expanded the authority for a pharmacist to dispense emergency refills. However, these allowances are often finite in nature and would end when the pandemic state of emergency ends. This paper seeks to analyze the laws and regulations in each state pertaining to the ability of a pharmacist to dispense an emergency refill when a patient’s prescription does not have refills and provide a recommendation to optimize the state legal and regulatory landscape to expand current allowances.
VOYAGE PLANNING AND TRACK KEEPING WITH PAPER AND ELECTRONIC CHARTS: A CASE STUDY OF MARITIME NAVIGATION TASKS.

Enhancements in shipboard automation offer the prospect of crew size reductions for navigation tasks. This work was concerned with comparing the structure of navigation tasks using paper charts with the same tasks accomplished using an electronic chart display information system (ECDIS). Voyage planning with paper charts is based on drawing specific voyage segments, measuring distances between waypoints, and annotating the chart with voyage specific information. These tasks change substantially with electronic charts, particularly in terms of how the task is accomplished. Similarly, the manual activities of track keeping are reduced, but the need for a continuous record maintains the use of the paper chart. For both navigation tasks, there is less ability to visualize geographic features continuously with electronic charts because of the keyhole effect created by a CRT display. It is concluded that the design of automated navigation aids should be based not only on the informational aspects of task perfor...
Resources for Teaching Discrete Mathematics: Early Writings on Graph Theory: Euler Circuits and The Königsberg Bridge Problem

In a 1670 letter to Christian Huygens (1629–1695), the celebrated philosopher and mathematician Gottfried W. Leibniz (1646–1716) wrote as follows: I am not content with algebra, in that it yields neither the shortest proofs nor the most beautiful constructions of geometry. Consequently, in view of this, I consider that we need yet another kind of analysis, geometric or linear, which deals directly with position, as algebra deals with magnitude. [1, p. 30] Known today as the field of ‘topology,’ Leibniz's study of position was slow to develop as a mathematical field. As C. F. Gauss (1777–1855) noted in 1833, Of the geometry of position, which Leibniz initiated and to which only two geometers, Euler and Vandermonde, have given a feeble glance, we know and possess, after a century and a half, very little more than nothing. [1, p. 30] The ‘feeble glance’ which Leonhard Euler (1707–1783) directed towards the geometry of position consists of a single paper now considered to be the starting point of modern graph theory. Within the history of mathematics, the eighteenth century itself is commonly known as ‘The Age of Euler’ in recognition of the tremendous contributions that Euler made to mathematics during this period. Born in Basel, Switzerland, Euler studied mathematics under Johann Bernoulli (1667–1748), then one of the leading European mathematicians of the time and among the first – along with his brother Jakob Bernoulli (1654–1705)–to apply the new calculus techniques developed by Leibniz in the late seventeenth century to the study of curves.
Simulated isobaric annealing

A simulated annealing algorithm for wire placement is proposed in which annealing is carried out under conditions of constant interconnection pressure rather than constant area. This is achieved by modifying the Metropolis criterion so that changes in the Gibbs free energy of the wires are calculated. This enables the area of the array devoted to wiring to decrease as the average wire length is reduced during the annealing schedule. The definition of interconnection pressure follows naturally from the thermodynamic interpretation of simulated annealing and it is shown to be equivalent to a wiring figure of merit called the channel density. The paper ends by speculating on the use of wire pressure to determine the phase transition temperature between the "gas" and "liquid" state of the system.
Reactions of coordinated ligands : VI. Reactions of cis-tetracarbonylbis-(chlorodiphenylphosphine)molybdenum(0) methylamine, p-toluidine, water, methanol, p-cresol, and ethanethiol and the subsequent reactions of the ammonolysis and hydrolysis products with chlorosilanes and boron trifluoride diethyletherate☆

Abstract The complex cis-[Mo(CO)4(PPh2Cl)2] (I) readily reacts with a variety of nucleophiles, HX where X  NH2, NHMe, NH-p-C6H4Me, OCH3, O-p-6H4Me, and SEt, in the presence of a nitrogen base to yield new cis-[Mo(CO)4(PPh2X)2] complexes. The reaction of cis-[Mo(CO)4(PPh2NH2)2 (II) first with n-BuLi and then with dichlorosilanes yields unique heterocyclic complexes. The reaction of I with H2O and Et3N yields [Et3NH]+ cis-[Mo(CO)4(PPh2O)2H]− (VIII) which is postulated to contain a symmetrically-bound hydrogen. The hydrogen may be replaced by a BF2 group by treatment with BF3 · OEt2 and with a Na+ by treatment with NaOH and Et4NCl. Reaction of VIII with dichlorosilanes yields complexes containing unique heterocyclic rings analogous to those obtained from II.1H NMR and infrared spectral properties of the new complexes are given.
Behavior of the idiotypic network in conventional immune responses: II. Affinity and heterogeneity of idiotypic and anti-idiotypic antibodies following immunization with T-independent and T-dependent antigens

Abstract The relative affinity and heterogeneity of affinity of idiotypic and anti-idiotypic antibodies in mice immunized with the T-independent antigen DNP-Ficoll and the T-dependent antigen DNPHGG were measured by a plaque inhibition assay. Idiotypic plaque-forming cells (PFC) were detected by a conventional assay utilizing DNP-coated SRBC. Anti-idiotypic PFC were detected with SRBC coated with affinity-purified anti-DNP antibody of rabbit origin. It was found that both idiotypic and anti-idiotypic antibodies elicited by immunization with the T-independent antigen had lower affinity and were less heterogeneous than the corresponding antibodies originating in mice immunized with the T-dependent antigen. In addition, the affinity and heterogeneity values of the idiotypic antibodies were correlated with the affinity and heterogeneity values of the anti-idiotypic antibodies from the same mice. This finding indicates that idiotypic and anti-idiotypic antibodies mutually regulate each other, thus pointing to internal immunoregulatory effects of the idiotypic network with respect to these parameters.
What if IP is abolished?: Does the charter of fundamental rights of the EU make any difference?

The article briefly considers the impact of the EU Charter of Fundamental Rights on the Protection of Intellectual Property.
Infrared Spectroscopy of Biological Fluids in Clinical and Diagnostic Analysis

The infrared (IR) spectrum of a mixture serves as the basis to quantitate its constituents, and a number of common clinical chemistry tests have proven to be feasible using this approach. This article reviews the IR spectroscopy-based analytical methods that have been developed for consideration as clinical assays, including serum analysis, urine analysis, amniotic fluid assays for the estimation of fetal lung maturity, and others. Because of the widespread interest in the potential for in vivo measurement of blood glucose using near-IR spectroscopy, a separate section is devoted to the analysis of glucose in whole blood. A related technique uses the IR spectrum of biomedical specimens directly as a diagnostic tool. For example, the spectra of serum and of synovial fluid have proven to be useful in the diagnosis of metabolic disorders and arthritis respectively, without explicitly recovering their chemical composition from the spectra. Rather, characteristic spectral features and patterns have been identified as the basis to distinguish spectra corresponding to healthy patients from those corresponding to diseased patients. These and other related applications to both human and veterinary health are reviewed here. Since diagnostic spectroscopy of cells and tissues are the subject of separate reviews within this volume, the scope of the present article is restricted to analytical and diagnostic spectroscopy of biological fluids. Issues such as ease of use, speed, reliability, sample size, and calibration stability all play important roles in governing the practical acceptability of IR spectroscopy-based analytical methods. To provide a framework to illustrate these issues, descriptions are included for the various procedures that have been explored to successfully wed IR spectroscopy to clinical chemistry. Finally, a recent development promises to broaden the applicability of IR spectroscopy in both clinical analytical and diagnostic applications; the combination of microfluidics (laminar fluid diffusion interface) with spectroscopy of biofluids is outlined with examples illustrating the potential for this integrated technique.
Characterization of amino acid transport during erythroid cell differentiation.

We have studied the changes in amino acid transport in fetal erythroid cells isolated from rat fetal liver at different gestation days. Our results show that System A transport as measured by the Na+-dependent uptake of 2-(methylamino)isobutyric acid (MeAIB) was conspicuous at day 13 but virtually disappeared between days 16 and 18. In contrast, the activity of System ASC measured by the Na+-dependent uptake of MeAIB-insensitive threonine uptake increased after day 14 and was optimal between days 16 and 18. This transport system regressed in activity with further maturation, but remained conspicuously saturable in the matured red blood cell. Interestingly, the newly discovered Na+-independent System asc (Vadgama, J. V., and Christensen, H.N. (1985) J. Biol. Chem. 260, 2912-2921), selective for the uptake of test substrates threonine, serine, and alanine, was present in these erythroid cells. Its activity increased during gestation days 16-18. System L transport was present simultaneously with the Na+-independent System asc. As we had previously demonstrated for the pigeon red blood cell, these two transport systems are kinetically independent as confirmed with inhibition studies and the special selectivity of System L to trans stimulation. Tryptophan uptake could be attributed predominantly to System L, as also observed for the nucleated pigeon red blood cells and certain other cells. Arginine showed its familiar Na+-independent mode of uptake as a cation throughout the interval of study. An exceptional Na+-dependent component of arginine uptake emerged after day 14, peaked at day 18, and then disappeared on further maturation of the erythroid cell.
Influence of metal exposure history on the bioaccumulation and subcellular distribution of aqueous cadmium in the insect Hydropsyche californica.

The influence of metal exposure history on rates of aqueous Cd accumulation, elimination, and subcellular distribution was examined in the aquatic insect Hydropsyche californica. Specimens were obtained from a reference site and a metal-contaminated site and returned to the laboratory where they were continuously exposed to aqueous Cd (518 ng/L, nominal) for 6 d, followed by 9 d of depuration. Rates of Cd accumulation and elimination were similar in insects from the two sites. Efflux rate constants, ke, ranged from 0.20 to 0.24/d (t1/2 ≈ 3 d). Immediately following exposure, the cytosol accounted for 40% of the body burden in insects from both sites; however, 89 ± 2% of the cytosolic Cd was associated with metallothionein-like proteins (MTLP) in insects from the contaminated site, compared to 60 ± 0% in insects from the reference site. The concentration of Cd bound to non-MTLPs (representing potentially Cd-sensitive proteins) was significantly greater in the insects from the reference site (134 ± 7 ng/g) than in those from the contaminated site (42 ± 2 ng/g). At the end of the depuration period, 90% of the accumulated Cd body burden had been eliminated, and Cd concentrations in MTLPs and non-MTLPs were similar between the sites. Results suggested that differences in exposure history had no influence on the bioaccumulation of Cd, but did affect the concentrations of Cd bound to MTLP during Cd exposure in these insects.
Social and functional variables associated with urinary tract infections in persons with spinal cord injury

Abstract Objective: Urinary tract infections (UTIs) and their complications remain a major source of morbidity and mortality after spinal cord injury (SCI). There has been much investigation into the physiological changes in persons with SCI and how these predispose to the development of UTIs, but other potentially influential variables are not so well understood. The purpose of this study is to examine behavioral, social, and functional factors and their relationship with UTIs. Our hypothesis is that lower UTI frequency will be associated with higher functional abilities, increased productivity, and higher life satisfaction scores. Design: Respondents to a mailed questionnaire reported information on demographics, bladder management methods, functioning, productivity, and life satisfaction. Patients: A volunteer sample from a list of all people with SCI previously treated at a university medical center rehabilitation medicine SCI inpatient service and/or outpatient SCI clinic from 1991 through 1994. Results: There were 81 (35%) responses to 229 received mailings. Mean reported UTIs were 1.37 (SD = 2.66) per year and 4.77 (SD = 6.70) over a 3-year period. UTIs per year and total UTIs over 3 years were negatively associated with functioning and productivity (number of hours worked per week), but were not associated with life satisfaction scores. Conclusion: As a result of this study there is an improved understanding of social and functional variables and how these may correlate with UTI incidence in this population. Further research into these variables is warranted.
Thyroxine and triiodothyronine turnover in the chicken and the bobwhite and Japanese quail

Abstract Except for the data of Heninger and Newcomer (1964) on the t 1 2 of T 4 and T 3 in cardiac tissue of chickens and brief reports on the t 1 2 of T 4 in blood plasma of chickens (Tata and Shellabarger, 1959 ; Hendrich and Turner, 1967) and Japanese quail (McFarland et al. , 1966) , no information has been found in the literature on the degradation of thyroid hormones in birds. In the present investigations, thyroxine- and triiodothyronine-distribution spaces (TDS) and biological half lives ( t 1 2 ) of the two hormones are reported. The extrathyroidal thyroxine- (ETT) and thyroid-secretion rate (TSR) from thyroxine degradation have been calculated from T 4 turnover data in the chicken, bobwhite and Japanese quail. Protein-bound iodine values (PBI) in the three species of birds are also presented. In addition, the results of TSR by thyroxine degradation are compared in chickens receiving diets adequate or deficient in iodine. Thyroxine and triiodothyronine turnover was studied in the chicken, bobwhite quail and Japanese quail. The thyroid secretion rate (TSR) as determined by this method in 7-week normal chickens, 7-week goitrogen-treated chickens, 56-week normal chickens, bobwhite, and Japanese quail, averaged 2.03, 1.59, 1.02, 2.49, and 2.78 μg/100 gm body weight/day, respectively. The TSR of iodine-deficient chickens was found to be significantly decreased. The representative biological half lives of T 4 in the blood of chickens, bobwhite, and Japanese quail were 3.25, 4.60, and 5.50 hours, respectively. The half life of T 3 in each species of birds tested is not significantly different. The representative thyroxine-distribution space (TDS) in ml/100 gm body weight of chickens, bobwhite, and Japanese quail, respectively, measured 29.39, 28.08, and 55.29. TDS/unit body weight of 56-week old chickens is significantly lower than in 7-week chickens. T 3 -distribution spaces in all birds are higher than that of T 4 . The representative protein-bound iodine of chickens, bobwhite, and Japanese quail were measured as 1.12, 1.76, and 1.26 μg, respectively. Increased plasma radioactivity was found in cardiac blood samples as compared to those taken by venous puncture. It is believed that this represents discharge of unchanged hormone from extrathyroidal tissues, probably the liver, in response to the withdrawal of a relatively large volume of blood. The possible role of this mechanism in regulating thyroid hormone levels is discussed.
Release of 14C-norepinephrine into the lateral cerebroventricle of rats by exposure to a conditioned aversive stimulus.

Abstract Rats chronically implanted with push-pull cannulas were injected with a pulse of 14 C-norepinephrine (NE) into the lateral cerebroventricle under a variety of pretreatment and behavioral conditions. Animals pretreated intraventricularly with 6-hydroxydopamine (Group A) or ascorbic acid vehicle (Group B) were subsequently perfused under four conditions: (1) presentation of a novel, visual stimulus in a one-way avoidance chamber; (2) presentation of the light (CS) followed by shock; (3) training to a high level of avoidance behavior, after which the CS was presented in the absence of opportunity for an avoidance response and in the absence of shock; and (4) after forced extinction, followed by CS without opportunity to avoid and without presentation of shock. Samples of perfusate from rats subjected to the four test conditions were analyzed by thin-layer chromatography for total 14 C in a scintillation counter and for proportion of NE and normetanephrine (NM). During Tests 1 and 4 the 14 C perfusion wash-out did not differ from control values for either Group A or B. During Test 2, total radioactivity as well as the proportions of NE and NM increased in the perfusate for both Groups A and B. Presenting the CS without shock (3) resulted in an increase in 14 C and NE and NM for Group B (vehicle), but not for Group A (6-OHDA). To test for non-specific release unrelated to a brain catecholaminergic function, another group of rats was subjected to identical treatments with the exception that 14 C-urea replaced 14 C-NE as a pulse-label. In these animals Test 2 (shock) induced an increase in 14 C in the perfusate, while Tests 1, 3 and 4 yielded wash-out curves essentially identical to controls.
The Society at a Crossroads: Milestones and Imperatives for Cancer Clinical Trials

The Society of Surgical Oncology (SSO) has evolved into the leading academic oncologic society for surgeons. Major contributions by members of the SSO include significant participation in cancer clinical trials and basic biomedical research, which should be maintained and enhanced. Progress with outcomes research for basic, translational, and clinical investigations must be sustained with supportive biomedical technology to complete clinical trials in Phases I–IV. Investment in the development and support of translational researchers is of paramount importance to the future of the discipline.
An Inhibitor of Protein Phosphorylation Stops the Circadian Oscillator and Blocks Light-Induced Phase Shifting in Gonyaulax polyedra:

The expression of circadian rhythmicity in Gonyaulax polyedra is strikingly altered by an inhibitor of protein phosphorylation. The effects of 6-dimethylaminopurine (6-DMAP), known to reversibly block cell division in many systems through inhibition of protein kinase activity, are described here for Gonyaulax. Its action appears to be exclusively tonic in nature; in cells continuously exposed, the period is lengthened in a concentration-dependent fashion. Shorter treatments at a higher concentration of 6-DMAP (5 mM) apparently stop the circadian oscillator, but reversibly so, since the rhythm resumes after drug removal with a phase delay approximately equal to the duration of the treatment. Pulses of the inhibitor are effective in causing phase delays at all times of the circadian cycle. In addition, 6-DMAP completely blocks light-induced phase advances and is effective in inhibiting many Gonyaulax protein kinases in vitro.
Towards Optimum Group Placement from the Perspective of Self and Group Experience

This paper offers the referring and the prospective group analyst/therapist a way of conceptualizing optimum placement. This approach, using the charts provided, aids in determining the patient's current needs based on past and present selfobject functions as well as deficits/derailments and traumatizations. The charts also offer the group analyst/therapist a tool with which to evaluate the present selfobject functions, impingements and trauma-tizations that may be available in a prospective group to determine if the match is as good as possible or `good enough', as well as determining whether group should be the treatment modality of choice. When the interviewing analyst/therapist has taken all of the current and past selfobject functions and traumatizations into account, the patient can be expected to benefit from the most growth-enhancing placement available.
Diversity and evolution of secondary metabolism in the marine actinomycete genus Salinispora

Access to genome sequence data has challenged traditional natural product discovery paradigms by revealing that the products of most bacterial biosynthetic pathways have yet to be discovered. Despite the insight afforded by this technology, little is known about the diversity and distributions of natural product biosynthetic pathways among bacteria and how they evolve to generate structural diversity. Here we analyze genome sequence data derived from 75 strains of the marine actinomycete genus Salinispora for pathways associated with polyketide and nonribosomal peptide biosynthesis, the products of which account for some of today’s most important medicines. The results reveal high levels of diversity, with a total of 124 pathways identified and 229 predicted with continued sequencing. Recent horizontal gene transfer accounts for the majority of pathways, which occur in only one or two strains. Acquired pathways are incorporated into genomic islands and are commonly exchanged within and between species. Acquisition and transfer events largely involve complete pathways, which subsequently evolve by gene gain, loss, and duplication followed by divergence. The exchange of similar pathway types at the precise chromosomal locations in different strains suggests that the mechanisms of integration include pathway-level homologous recombination. Despite extensive horizontal gene transfer there is clear evidence of species-level vertical inheritance, supporting the concept that secondary metabolites represent functional traits that help define Salinispora species. The plasticity of the Salinispora secondary metabolome provides an effective mechanism to maximize population-level secondary metabolite diversity while limiting the number of pathways maintained within any individual genome.
Exploring protein interactions.

Abstract Protein Targeting Protocols Edited by Robert A. Clegg. Totowa, Humana, 1998, $79.50 (xii+ 331 pages), ISBN 0-896-03450-X
Inferior olive serotonin and norepinephrine levels during development in the genetically dystonie rat

Abstract The dystonic ( dt ) rat is an autosomal recessive mutant with a motor syndrome that shares several features with idiopathic torsion dystonia in humans. In the dt rats, marked biochemical and physiological abnormalities have been localized to the olivo-cerebellar system. At the pharmacological level, the dt rats exhibit enhanced sensitivity to the behavioral effects of serotonergic (5HT) agonists, including quipazine, a drug that activates the neurons of the inferior olive (IO). High performance liquid chromatography with electrochemical detection was used to assay 5-HT, 5-hydroxyindoleacetic acid (5HIAA), and norepinephrine (NE) in micropunches of the IO in normal and dt rats at 14, 18 and 22 days of age. Samples of the rostral frontal lobes were used as internal controls. Significant age-dependent effects were seen on 5-HT and 5-HIAA levels in the IO, but not the frontal cortex, in both groups. Although both groups reached similar 5-HT levels by postnatal day 22, a significant interaction effect between age and phenotype indicated a difference in the pattern of development. Administration of quipazine (10 mg/kg, IP) to 18-day-old normal and dt rats l h prior to sacrifice caused significant reductions in NE, 5-HIAA and the ratio of 5-HIAA to 5-HT; however, no phenotypic differences were detected. The findings do not suggest that the differential behavioral responses to 5-HT agonists seen in normal and dt rats are the result of global abnormalities in 5-HT systems, nor do they suggest the presence of presynaptic defects in the IO. The age-dependent differences in 5-HT levels in the IO may, however, indicate a developmental abnormality in the 5-HT innervation of this structure in the dt rat. Serotonin Norepinephrine Inferior olive Dystonia 5-hydroxyindoleacetic acid Quipazine
Democratic theory in library information science

A recent article by Joseph Buschman regrets that democratic theory is an unfinished idea. The argument appears to assume an essential relationship between library and information science (LIS) and democratic theory. Libraries services are important for undemocratic purposes also, and like other sociotechnical systems, partake on the cultural context in which they are deployed. © 2008 Wiley Periodicals, Inc.
Cardiac implantable electronic device lead extraction in patients with underlying infection using open thoracotomy or percutaneous techniques.

Background: Explanting infected cardiac implantable electronic devices (CIEDs) and extracting their associated leads can be performed percutaneously (EP) or via open-thoracotomy (OR) approach. In this study, we examined the characteristics and outcomes of infected CIED patients undergoing EP vs. OR extraction procedures. Methods: All patients (EP: n = 329 and OR: n = 24) who received lead extraction in the presence of an infected CIED from 2005 to 2010 at the University of Pittsburgh Medical Center were included in this study. Demographic and clinical characteristics were obtained from the electronic medical records. The Charlson comorbidity index (CCI) was used to adjust for severity of co-morbid conditions. Results: Compared to the EP group, OR patients were more likely to have positive blood cultures, larger vegetations, and worse CCI scores. They also had higher total mortality rates at 1 (p = 0.036), 6 (p = 0.020), and 12 months (p = 0.012) after the procedure. One-year survival after lead extractions was significantly better for the EP compared to the OR group (p = 0.002) even after adjusting for other comorbid illnesses (HR = 2.6, p = 0.010) in a Cox regression model. Conclusions: Infected CIED patients undergoing open-chest lead extraction are sicker and have higher mortality rates compared to those undergoing percutaneous extraction. Randomized, prospective data are needed to determine whether the procedural strategy for lead extraction accounts in part for the difference in outcome.
Enhanced magnification endoscopy in the upper gastrointestinal tract.

Abstract In diseases such as Barrett's esophagus and celiac disease, the mucosal abnormality is patchy or irregular, highlighting the need for targeted biopsies. Enhanced magnification endoscopy is an effective, readily available method that can be used to assist in target biopsies and endoscopic diagnosis leading to an endoscopic classification system. The technique is not difficult and adds only an additional 5 to 10 minutes to a standard endoscopic procedure;however, most endoscopists never receive instruction in magnification endoscopy during their training. The value of this technique is still being explored, but the improvement in diagnostic accuracy will have an impact on decreasing morbidity and mortality without a large increase in cost. Increased use of this technique will aid in the diagnosis of celiac disease and simplify the classification system for Barrett's esophagus. Using enhanced magnification endoscopy at multiple centers in studies will help to determine the intra- and inter-observer variability, define the endoscopic criteria for dysplasia and early neoplastic changes, and standardize the visualized mucosal patterns more clearly.
Half-site editing: an in vitro mutagenesis procedure for truncating a DNA fragment and introducing a new restriction site.

Abstract Half-site editing is an in vitro mutagenesis procedure designed for use in making precise plasmid constructions. Like many in vitro mutagenesis techniques, this procedure involves hybridization of a mutagenic oligonucleotide primer to single-stranded template DNA followed by polymerization with DNA polymerase I (Klenow). Half-site editing differs from other techniques in two main ways. First, T4 DNA polymerase treatment truncates the target DNA at a point determined by the primer and repairs any mismatches to the sequence specified by the primer. Second, a bluntend ligation step is included. This ligation exploits the symmetry inherent in most restriction sites to create a desired restriction site at the truncated end of the target DNA fragment. Half-site editing has been used to place ClaI restriction sites at the 3′ end of the yeast pyruvate kinase promoter and at two positions at the 5′ end of the yeast acetolactate synthase coding sequence.
Ophthalmic disease in Western Samoa.

Since the last report on eye disease in Western Samoa in 1959 by Dr Elliott, the population has increased from 97 000 to 158 000 The country now has a full-time ophthalmologist but could benefit from a larger eye care service. The distribution of disease is very similar to that found in 7959, with pterygium, cataract and injuries comprising the most frequent eye problems Acute angle-closure glaucoma is much more common than open-angle glaucoma and is associated with a plateau ins configuration.
Comparison of coagulation factor XIII content and concentration in cryoprecipitate and fresh-frozen plasma.

Background For patients with plasma coagulation factor XIII (pFXIII) deficiency, recommended means of replacement include infusions of fresh-frozen plasma (FFP), cryoprecipitate, or (where available) factor (F)XIII concentrates. Quantitative differences in pFXIII concentration in FFP and cryoprecipitate are not well defined and were, therefore, the subject of this study. Study design and methods FFP and cryoprecipitate (10 bags each from blood group O donors) were analyzed to quantify pFXIII activity and antigen. Coagulation FVIII, fibrinogen, and von Willebrand factor (VWF) were also quantitated. Results Mean (+/-SD) pFXIII activity in cryoprecipitate and FFP bags was 60 +/- 30 and 288 +/- 77 U per bag, respectively, and pFXIII antigen and activity levels were concordant. Other comparisons (mean +/- SD) between cryoprecipitate and FFP, respectively, were as follows: coagulation FVIII activity, 133 +/- 37 and 265 +/- 83 U per bag; fibrinogen content (Clauss kinetic assay), 183 +/- 44 and 725 +/- 199 mg per bag; VWF antigen content, 181 +/- 53 and 218 +/- 70 U per bag; VWF ristocetin cofactor activity, 168 +/- 34 and 221 +/- 65 U per bag; VWF collagen-binding activity, 164 +/- 40 and 208 +/- 71 U per bag; and fluid (plasma) volumes per bag, 21.3 +/- 2.7 and 245 +/- 29 mL. Conclusion In contrast to other cryoprecipitable coagulation proteins, pFXIII is only mildly enriched in cryoprecipitate when compared with FFP (approx. two- to threefold). Although both products can provide effective pFXIII replacement, FFP may be preferred when infusion volume is not a major consideration and pFXIII concentrates are not available. VWF is substantially enriched in cryoprecipitate (approx. ninefold compared with its concentration in FFP), with VWF activity content exceeding that of FVIII by approximately 26 percent on average.
Increased UVA exposures and decreased cutaneous Vitamin D3 levels may be responsible for the increasing incidence of melanoma

Cutaneous malignant melanoma (CMM) has been increasing at a steady exponential rate in fair-skinned, indoor workers since before 1940. A paradox exists between indoor and outdoor workers because indoor workers get three to nine times less solar UV (290-400 nm) exposure than outdoor workers get, yet only indoor workers have an increasing incidence of CMM. Thus, another "factor(s)" is/are involved that increases the CMM risk for indoor workers. We hypothesize that one factor involves indoor exposures to UVA (321-400 nm) passing through windows, which can cause mutations and can break down vitamin D(3) formed after outdoor UVB (290-320 nm) exposure, and the other factor involves low levels of cutaneous vitamin D(3). After vitamin D(3) forms, melanoma cells can convert it to the hormone, 1,25-dihydroxyvitamin D(3), or calcitriol, which causes growth inhibition and apoptotic cell death in vitro and in vivo. We measured the outdoor and indoor solar irradiances and found indoor solar UVA irradiances represent about 25% (or 5-10 W/m(2)) of the outdoor irradiances and are about 60 times greater than fluorescent light irradiances. We calculated the outdoor and indoor UV contributions toward different biological endpoints by weighting the emission spectra by the action spectra: erythema, squamous cell carcinoma, melanoma (fish), and previtamin D(3). Furthermore, we found production of previtamin D(3) only occurs outside where there is enough UVB. We agree that intense, intermittent outdoor UV overexposures and sunburns initiate CMM; we now propose that increased UVA exposures and inadequately maintained cutaneous levels of vitamin D(3) promotes CMM.
Laser metrology gauges for OSI

Heterodyne interferometers have been commercially available for many years. In addition, many versions have been built at JPL for various projects. This activity is aimed at improving the accuracy of such interferometers from the 1 - 30 nanometer level to the picometer level for use in the proposed OSI and SONATA missions as metrology gauges. In the null-gauge configuration, we obtained a precision of 0.6 picometers at time scales of 2,500 seconds. In the relative-gauge configuration, we obtained an accuracy of 3.5 picometers rms in vacuum at time scales of few minutes. As absolute gauge with an accuracy of 10 microns over a distance of 10 meters in under construction.
In situ laser fenestration for revascularization of the left subclavian artery during emergent thoracic endovascular aortic repair.

PurposeTo present midterm outcomes of thoracic endovascular aortic repair (TEVAR) with laser fenestration to revascularize the left subclavian artery (LSA) as an alternative to debranching.MethodsS...
Long‐term prospects for US housing markets: Fewer units, greater investment

Abstract Demographic factors that stimulated robust housing markets in past decades will weaken the future demand for new residential construction. The baby boom generation will reach middle‐age, well past the age of entry into the market. Changing social factors, such as marriage and divorce rates and women's labour force participation, will also have an effect on future housing demand. Four major trends, analysed in the paper, will increase demand for quality and increased investment per dwelling unit, thus offsetting the declining demand for new units. First, the baby boom generation will reach their peak lifetime earning period in the years ahead and their discretionary incomes will be large. Second, largely as the result of a benevolent public policy, the elderly have gained substantially in affluence, enabling them to live independently and to upgrade their physical housing standards. Third, it is expected that household technology will be increasingly demanded as time costs rise. Finally, the ‘serv...
Correlation of lactate and pH in human skeletal muscle after exercise by 1H NMR

We have made in vivo 1H NMR measurements of the time course of pH and lactate in human skeletal muscle after exercise. Spectra were obtained in a 4.7-T 30-cm bore Bruker Biospec spectrometer with a 2.5-cm diameter single surface coil. pH was determined from the shift of the endogenous carnosine H-C2 peak while lactate concentrations were determined by comparison with endogenous total creatine, taken to be 28.5 mM/kg wet wt. Fitting the data shows that the exponential decay of lactate (-0.094 +/- 0.014 min-1. t1/2 = 10.6 min) is slower than that of pH (-0.147 +/- 0.015 min-1, t1/2 = 4.7 min), n = 7 with two different volunteers. These values are significantly different with P less than 0.0005. Relaxation times of lactate and creatine were also measured for lactate quantitation; creatine T1, 1.23 +/- 12 s, T2, 136.2 +/- 26.4 ms (both in resting human muscle); lactate T1 (in postmortem rabbit muscle), 1.0 +/- 11 s and T2, 80 ms (in postexercise human muscle). At the end of intense exercise, the lactate level reached was 25.3 +/- 4.0 mM and the average pH drop was 1.0 pH unit. We discuss the implications of these measurements in conjunction with existing data on other sources of H+ flux, phosphocreatine resynthesis, H+ transport, and contribution of inorganic phosphate to buffering.
Flow Structure in the Wake of a Wishbone Vortex Generator

The results of an experimental examination of the vortex structures shed from a low-profile «wishbone» generator are presented. The vortex generator height relative to the turbulent boundary layer was varied by testing two differently sized models. Measurements of the mean three-dimensional velocity held were conducted in cross-stream planes downstream of the vortex generators. In all cases a counter-rotating vortex pair was observed. Individual vortices were characterized by three descriptors derived from the velocity data: circulation, peak vorticity, and cross-stream location of peak vorticity. Measurements in the cross plane at two axial locations behind the smaller wishbone characterize the downstream development of the vortex pairs