cssi/SciSciGPT-SciSciNet huggingface dataset:
Glucose alone does not completely hydrate bacteriorhodopsin in glucose-embedded purple membrane.

SUMMARY Glucose embedding is a simple and highly effective method for preparing biological macromolecules for high-resolution electron microscopy. The investigation of conditions that can trap the M-state intermediate in the bacteriorhodopsin (bR) photocycle has revealed, however, that when glucose-embedded bR is prepared at ambient humidity, it does not fully retain the capability to execute a proper photocycle. However, ‘native’ photocycle properties are returned after glucose-embedded samples are equilibrated at 81% relative humidity. Equilibration at relative humidities significantly higher than 81% causes glucose to dissolve in its own water of hydration, resulting in samples that may be too thick to be suitable for electron microscopy. The results obtained with bR indicate that caution should be taken with other biological specimens, and it cannot be assumed that glucose-embedded biological macromolecules retain completely their native, hydrated structure, even when high-resolution electron diffraction patterns are obtained. Equilibration of such samples at high humidity may generally be a worthwhile precaution when using the glucose-embedding technique.
Beyond cognitive ability: Improving the prediction of performance

New measures of practical intelligence and personality traits were assessed for their ability to improve the prediction of performance beyond cognitive ability. Measures of practical intelligence from the newly developed Constructive Thinking Inventory and traits measuring emotional stability and expedience were used as independent variables in regression analyses predicting academic performance, training performance and leadership ratings of 86 student leaders. The constructive thinking scales added significantly to the prediction of academic performance, beyond measures of cognitive ability. Constructive thinking also accounted for unique variance predicting training performance and leadership ratings. Personality traits were unrelated to performance or leadership.
Effects of hyperbaric oxygen on the replanted extremity subjected to prolonged warm ischaemia

In this investigation, the influence of hyperbaric oxygen (HBO) therapy on the survival of a replanted extremity subjected to prolonged warm ischaemia is evaluated. Among the relative contraindications to replantation are prolonged warm ischaemia time, since an obstruction to blood reflow ('no-reflow phenomenon') may occur in amputated parts that are subjected to more than 6h of warm ischaemia. Twenty-three rat hindlimbs were amputated and subjected to 4h of normothermic ischaemia. The average weight of the animals was 500 gm, and re-plantation of the hindlimb was performed by bone fixation followed by microvascular anastomosis of the femoral vessels. Limb re-vascularisation was confirmed at the end of all procedures by the milk test, clinical assessment and pulse oximetry recordings (>90%). Eleven animals served as a control group and no further therapy was instituted, whereas 12 animals served as the study (replantation) group and were subjected to HBO therapy for 3 days postoperatively. The therapy was conducted in a large animal chamber for 90 min at 2.5 ata. Limb survival was assessed by capillary refill upon compression, skin turgor assessment and colour. Confirmation of clinical findings was conducted with daily pulse oximetry readings of >90%. Animals were followed up for 7 days at which point all animals were euthanized or were euthanized earlier if a non-viable limb was present. Two of the 11 limbs in the control group survived following re-plantation, whereas eight of the 12 limbs in the experimental HBO group survived at least 7 days following replantation. This difference was statistically significant (p=0.0361) using chi-square analysis and Fisher's exact test. Although re-plantation of an amputated extremity after prolonged warm ischaemia is considered a relative contraindication due to the possibility of poor outcomes, our results indicate that the window for replantation may be increased if adjunctive HBO therapy is employed in the postoperative period.
Oriented Markov random field based dendritic spine segmentation for fluorescence microscopy images.

Dendritic spines have been shown to be closely related to various functional properties of the neuron. Usually dendritic spines are manually labeled to analyze their morphological changes, which is very time-consuming and susceptible to operator bias, even with the assistance of computers. To deal with these issues, several methods have been recently proposed to automatically detect and measure the dendritic spines with little human interaction. However, problems such as degraded detection performance for images with larger pixel size (e.g. 0.125 μm/pixel instead of 0.08 μm/pixel) still exist in these methods. Moreover, the shapes of detected spines are also distorted. For example, the “necks” of some spines are missed. Here we present an oriented Markov random field (OMRF) based algorithm which improves spine detection as well as their geometric characterization. We begin with the identification of a region of interest (ROI) containing all the dendrites and spines to be analyzed. For this purpose, we introduce an adaptive procedure for identifying the image background. Next, the OMRF model is discussed within a statistical framework and the segmentation is solved as a maximum a posteriori estimation (MAP) problem, whose optimal solution is found by a knowledge-guided iterative conditional mode (KICM) algorithm. Compared with the existing algorithms, the proposed algorithm not only provides a more accurate representation of the spine shape, but also improves the detection performance by more than 50% with regard to reducing both the misses and false detection.
Spatial patterns of Holocene glacier advance and retreat in Central Asia

Glaciers in the southern Himalayas advanced in the early Holocene despite an increase in incoming summer solar insolation at the top of the atmosphere. These glacier advances are in contrast to the smaller alpine glaciers in the western and northern regions of Central Asia. Two different glacier mass-balance models are used to reconcile this Holocene glacier history with climate by quantifying the change in equilibrium-line altitudes (ELA) for simulated changes in Holocene climate. Both ELA models clearly show that the lowering of ELAs in the southern Himalayas is largely due to a decrease in summer temperatures, and that an increase in monsoonal precipitation accounts for less than 30% of the total ELA changes. The decrease in summer temperatures is a dynamic response to the changes in solar insolation, resulting in both a decrease in incoming shortwave radiation at the surface due to an increase in cloudiness and an increase in evaporative cooling. In the western and northern zones of Central Asia, both ELA models show a rise in ELAs in response to a general increase in summer temperatures. This increase in temperatures in the more northern regions is a direct radiative response to the increase in summer solar insolation.
Evidence of direct smooth muscle relaxant effects of the fibrate gemfibrozil.

Fibrates are commonly employed to treat abnormal lipid metabolism via their unique ability to stimulate peroxisome proliferator-activated receptor alpha (PPARα). Interestingly, they also decrease systemic arterial pressure, despite recent evidence that PPAR α may contribute to expression of renin and related hypertension. Yet, mechanisms responsible for their potential antihypertensive activity remain unresolved. Rapid decreases in arterial pressure following bolus intravenous injections of bezafibrate strongly suggest they may relax arterial smooth muscle directly. But since bezafibrate is highly susceptible to photodegradation in aqueous media, it has never been critically tested for this possibility in vitro with isolated arterial smooth muscle preparations. Accordingly, we tested gemfibrozil which is resistant to photodegradation. We examined it over a therapeutically-relevant range (50–400 μM) for both acute and delayed relaxant effects on contractions of the isolated rat tail artery; contractions induced by either depolarizing its smooth muscle cell membranes with high potassium or stimulating its membrane-bound receptors with norepinephrine and arginine-vasopressin. We also examined these same gemfibrozil levels for effects on spontaneously-occurring phasic rhythmic contractile activity, typically not seen in arteries under in vitro conditions but commonly exhibited by smooth muscle of uterus, duodenum and bladder. We found that gemfibrozil significantly relaxed all induced forms of contraction in the rat tail artery, acutely at the higher test levels and after a delay of a few hours at the lower test levels. The highest test level of gemfibrozil (400 μM) also completely abolished spontaneously-occurring contractile activity of the isolated uterus and duodenum and markedly suppressed it in the bladder. This is the first evidence that a fibrate drug can directly relax smooth muscle contractions, either induced by various contractile agents or spontaneously-occurring. These findings are particularly relevant to both the recently renewed concern over the impact of fibrates on hypertension and a new understanding of their gastrointestinal side effects.
Dose-Related Effects of Cigarette Smoking on Olfactory Function

Little is known about the influence of cigarette smoking on the ability to smell; previous studies on this topic have led to contradictory findings and have failed to take into account smoking dose and duration. In the present study, the 40-odorant University of Pennsylvania Smell Identification Test was administered to 638 subjects for whom detailed smoking histories were available. Smoking was found to be adversely associated with odor identification ability in a dose-related manner in both current and previous cigarette smokers. Among previous smokers, improvement in olfactory function was related to the time elapsed since the cessation of smoking. Logistic regression analysis found current smokers to be nearly twice as likely to evidence an olfactory deficit than persons who have never smoked. Overall, the data suggest that (1) smoking causes long-term but reversible adverse effects on the ability to smell and (2) the failure of some studies to demonstrate smoking effects may be caused by the inclusion of persons with a history of smoking in the nonsmoking groups. ( JAMA . 1990;263:1233-1236)
Lens-induced glaucoma.

The crystalline lens is implicated as a causative element in producing several forms of glaucoma. Etiologically they represent a diversity in the presentation of the glaucomatous process. These conditions include glaucoma related to: lens dislocation (ectopia lentis), lens swelling (intumescent cataract), classical pupillary block, aqueous misdirection - ciliary block, phacoanaphylaxis, lens particle, and phacolytic glaucoma. The management of elevated intraocular pressure often requires altering the intraocular relationship of anatomic structures surrounding the lens or lens removal. We will review the entities that produce these lens-induced glaucomatous conditions and suggest a rational approach to their diagnosis and treatment.
Production of migration-inhibitory factor by a human T-lymphoblast cell line☆

Abstract Migration-inhibitory-factor (MIF) activity was detected in culture supernatants of the human T-lymphoblast cell line Mo after stimulation with phytohemagglutinin and phorbol myristate acetate. MIF activity was not detected in unstimulated cultures reconstituted with phytohemagglutinin and phorbol myristate acetate. Conditioned medium from the cell line Mo was fractionated by Sephadex G-100 gel nitration. MIF-containing Sephadex fractions corresponding to a M r , of 60,000 to 70,000 were further fractionated by isoelectrofocusing, resulting in a sharp peak of activity with a p I of 4.6 to 5.2. This MIF species constitutes a major form secreted by Mo cells; it adheres to Con A-Sepharose, is trypsin-resistant, and is denser than pure protein as determined by CsCl density gradient centrifugation. These are the same physicochemical characteristics previously established for second-day pH5-MIF from peripheral blood mononuclear cells (W. Y. Weiser et al., J. Immunol. 126 , 1958, 1981). In contrast, Sephadex fractions corresponding to larger molecules ( M r 70,000–90,000) contain at least two additional MIF species. These larger MIF forms have a p I of 3.0 to 3.5 and of 4.6 to 5.2 and lack affinity to Con A-Sepharose. Thus, the Mo T-cell line produces large quantities of at least three different species of human MIF.
Diplochory in western chokecherry: you can't judge a fruit by its mesocarp.

Western chokecherry (Prunus virginiana var. demissa, Rosaceae) is dispersed by frugivorous birds and carnivores, but it has large seeds that are potentially attractive to rodents that could act as seed predators and dispersers. Here, we quantify the benefits of primary dispersal by birds and secondary dispersal by scatter-hoarding rodents. In the fall, avian frugivores (mostly American robins, Turdus migratorius, and cedar waxwings, Bombycilla cedrorum) consumed 87% of the fruit crop and dispersed 67% of the fruit crop away from parent plants. Rodents removed 89% of seeds that simulated bird-dispersed seed rain from transects in riparian zones and 58% from transects in upland habitats. Rodents scatter-hoarded 91.6% of the seeds they removed, burying most in small caches (two to eight seeds) 8–25 mm deep. About 39% of the seeds in spring caches produced seedlings. Inside rodent-proof exclosures, 52.1% of seeds buried to simulate rodent caches produced seedlings, 29.7% of which were still alive after 1 year. In contrast, only 3.8% of seeds placed on the soil surface, simulating dispersal by avian frugivores, produced seedlings. Seed dispersal by frugivorous birds likely contributes to colonization of unoccupied habitat through long-range dispersal and to escape from distance-dependent seed mortality near the parent plant. Despite seed losses, rodents offer short-range seed dispersal and bury seeds in more favorable sites for germination, improving seedling emergence and establishment. The combined mechanisms of seed dispersal significantly enhanced chokecherry seedling recruitment by providing more dispersal-related benefits than either frugivorous bird or scatter-hoarding rodents could provide alone.
Expansion of Amish Dairy Fanning in Wisconsin

Amish farmers now manage over 5% of Wisconsin's dairy herds. In contrast with the steady declines in the total number of dairy farmers, the number of Amish dairymen in Wisconsin has increased by 80% since 1989. Drawing upon Dairy Producer License data, a recently published Amish directory, and surveys of local agricultural officials and Amish ministers, this paper examines the current status and distribution of Amish dairy farming in Wisconsin and southeastern Minnesota. The changes in the dairy farm landscape resulting from the rapid expansion of the Amish, which are most conspicuous near cheese factories that accept milk in cans, are also described.
Electron-beam lithography for micro and nano-optical applications

Direct-write electron-beam lithography has proven to be a powerful technique for fabricating a variety of micro- and nano-optical devices. Binary E-beam lithography is the workhorse technique for fabricating optical devices that require complicated precision nano-scale features. We describe a bi-layer resist system and virtual-mark height measurement for improving the reliability of fabricating binary patterns. Analog E-beam lithography is a newer technique that has found significant application in the fabrication of diffractive optical elements. We describe our techniques for fabricating analog surface-relief profiles in E-beam resist, including some discussion regarding overcoming the problems of resist heating and charging. We also describe a multiple-field-size exposure scheme for suppression of field-stitch induced ghost diffraction orders produced by blazed diffraction gratings on non-flat substrates.
David Riesman and The Lonely Crowd

The reception of David Riesman’s classic sociological work The Lonely Crowd exemplifies both the possibilities and perils of the work of public intellectuals. The book was almost universally misread as a paean to inner-direction, and a lament upon the decline of the independent American spirit. But it was something rather more different, and more complex, than either of these things.
Codes of Medical Ethics and the Exportation of Less-Than-Standard Care

Recently a number of AIDS/AZT research studies, carried out by U.S. universities, have come under intense ethical scrutiny. In these studies, control groups of HIV-positive pregnant women were being given a placebo rather than AZT. Such research protocols would be illegal if practiced in the U.S. I examine a number of lamentable ethical lapses in the studies, and conclude that at least some of these ethical problems are traceable to a troubling contradiction between differing international codes of ethics. In a word, some international codes mandate that all research subjects (including control groups) receive the best standard of care available in the country sponsoring the research, while others suggest that providing only a "local" standard of care is ethically appropriate. I argue that these two ethical mandates cannot both be satisfied, and that host country populations will remain subject to exploitation unless this contradiction is resolved.
A Consensus Calibration based on TMI and Windsat

The Global Precipitation Measurement (GPM) mission requires a high degree of consistency among the microwave radiometers in the constellation which, in turn, demands a standard against which all the sensors can be compared. Ultimately this standard will be the GPM Microwave Imager, but for the present the TRMM Microwave Imager (TMI) fills this need. Since its calibration leaves much to be desired, a refinement using Windsat has been developed. This article defines the Consensus Calibration 1.1 which is applied to the TMI. In turn the TMI serves as a transfer standard to other satellite radiometers.
A syntactic theory of sequential state

Abstract The assignment statement is a ubiquitous building block of programming languages. In functionally oriented programming languages, the assignment is the facility for modeling and expressing state changes. Given that functional languages are directly associated with the equational λ-calculus-theory, it is natural to wonder whether this syntactic proof system is extensible to imperative variants of functional languages including state variables and side-effects. In this paper, we show that such an extension exists, and that it satisfies variants of the conventional consistency and standardization theorems. With a series of examples, we also demonstrate the system's capabilities for reasoning about imperative-functional programs and illustrate some of its advantages over alternative models.
Soil-structure interaction and imperfect trench installations for deeply buried concrete pipes

The imperfect trench installation method is used to reduce earth pressure on buried concrete pipes. Few quantitative refinements to the imperfect trench installation method, however, have been added since the fundamental mechanics of the reverse arching action were proposed by Marston and Spangler. There have been limited research results published regarding, primarily, qualitative aspects of earth load reduction for imperfect trench conditions. This paper identifies variables that significantly affect earth loads, as well as the effects of bedding and sidefill treatments. An optimum geometry for imperfect trench installations with regard to a soft material zone is presented to maximize the earth load reduction effects. The optimization process was based on parametric studies of the geometry and location of the soft zone, bedding, and sidefill treatments to reduce earth pressures. Predictor equations for earth load reduction rates were formulated incorporating the optimum geometry for the soft zone and bedding and sidefill treatments.
Comparison of Approximate Confidence Intervals for the Exponential Scale Parameter from Sample Quantiles

Several authors have considered point and interval estimation of the exponential scale parameter, σ, on the basis of subsets of the order statistics. In this paper, we suggest a procedure for finding approximate confidence intervals for σ in large samples, using k sample quantiles of a random sample of size n. The procedure is based on a simple chi-square approximation to the distribution of the asymptotically best linear estimate of σ. We compare this procedure with the one given by Ogawa (1962) based on an approximating t-distribution. We find that the interval based on the chi-square approximation is easier to calculate, and performs better when k is small and n is large.
The Impact of Leakage to the Power Supply Impedance of a Microprocessor

This paper shows that the resonant behavior of a microprocessor's power supply is strongly influenced by both the leakage and the dynamic power of the microprocessor. As a result of this, the peak package power supply impedance is a function of the operating conditions of the microprocessor. Measurements on a 65 nm Intelreg Pentiumreg 4 microprocessor have been used to quantify this behavior
Nadine Gordimer: The White Artist as A Sport of Nature

This article applies principles of new historicism to show that A Sport of Nature can be read as Gordimer's attempt to persuade South African artists to reject mere protest art and to shift art beyond the trap of oppositional forces in South Africa's history today. The text calls instead—via fiction and the imagination—for a new post-apartheid art that will generate creative possibilities for a future South Africa. Gordimer's protagonist, Hillela Capran, is read as a metaphor for the white South African artist who, like Hillela, struggles for an authentic identity and meaningful role in the evolving history of South Africa. This paper asserts that A Sport of Nature boldly proposes the mutation necessary for the South African artist and people to resolve the political, personal, or artistic fragmentation, beckoning other artists along the path. Hope of its assured success, however, remains as elusive and unpredictable as any "sport of nature" must be. This article is available in Studies in 20th Century Literature: http://newprairiepress.org/sttcl/vol15/iss1/13 Nadine Gordimer: The Artist as A Sport of Nature' Barbara Temple-Thurston Pacific Lutheran University Nadine Gordimer, South Africa's most renowned fiction writer and recipient of many international awards, published her ninth novel in 1987. While all her fiction and her non-fiction comment profoundly on the psychological, political, and historical impact of apartheid on South Africa's people and society, her most recent novel, A Sport of Nature, is the most historically and geographically panoramic of all her works.' Gordimer's astute and reflexive historical consciousness, by now a fact well-established through Stephen Clingman's seminal work, The Novels of Nadine Gordimer, and through Gordimer's own non-fictional commentaries, is most clearly evident in this recent novel. A Sport of Nature demands a reader who acknowledges Gordimer's acute consciousness of the processes of history. Confusion over the novel has resulted from a failure to read the text in terms of the dialectic between the personal, the political, and the historical. Grounding one's reading in the new historicist approach allows the reader to recognize Gordimer's call for the emergence of a new artistic consiousness that shapes, yet in turn is shaped by, historical conditions-a consciousness that posits a new post-apartheid art. New historicism, as Louis Montrose sees it, is "new in its refusal of unproblematized distinctions between 'literature' and 'history,' between 'text' and context'; new in resisting a prevalent tendency to posit and privilege a u. ified and autonomous individual-whether an Author or a Work-to be set against a social or literary background" (6). The intertextuality of A Sport of Nature embodies this view through its incorporation of historical figures like Mandela, Nkomo, Luthuli, through movements like the African National Congress, and through cameo appearances of characters like Rosa Burger from Gordimer's earlier fiction.
A Comprehensive Model for Predicting Fatigue Life of Laser Welded Lap Joint of Galvanized High Strength Steel as a Function of Residual Stresses

This paper presents a three-dimensional (3D) multi-physics finite element model (FEM) to predict the fatigue life of a laser welded lap joint of dual phase (DP) 980 steel sheets based upon the level of residual stress. A FEM-based thermal analysis is first performed to numerically predict the welding-induced temperature field combined with the corresponding experimental verification. The temperature histories are then loaded into the mechanical model as thermal loading to numerically calculate the evolution curves of thermally induced stress in order to calculate the level of residual stresses after cooling to room temperature. In order to calculate the equivalent fatigue strength in the laser-welded lap joint, the resultant multi-axial stress (including the induced residual stress (RS) result) is loaded into the equivalent uni-axial stress equation via the Sine Method (SM) in order to achieve the stress curve as a function of the loading cycles. A series of fatigue tests of lap joints are also performed in order to achieve the S-N curves, from which an empirical function between the alternating stress and loading cycle is derived in order to predict the fatigue life of the DP980 lap joint. Finally, the maximum fatigue strength can be predicted numerically through the proposed FEM instead of using experimental trials. The numerical results show that a greater temperature gradient and residual stress are mainly located within the fusion zone (FZ) and close to the heat affected zone (HAZ). The residual stress plays an important role in deciding the final fatigue strength and failure of the DP980 lap joint. An X-ray diffraction technique is used to experimentally measure the residual stress distribution within the weld, for which the numerically predicted results exhibit a good agreement. Also, the numerical simulation and experimental measurements of the fatigue life versus the applied load show a good correlation of results.Copyright © 2012 by ASME and General Motors
Experimental determination of low order structure factors in the intermetallic compound TiAl

Abstract Rocking curves from several low order reflections in TiAl were recorded in digitized form using energy-filtered convergent beam electron diffraction in a transmission electron microscope. The low order reflections studied were 001, 002, 200, 111, 110, 220, 202, 113, and 311. These experimental rocking curves were simulated using computations based on the dynamic theory of electron diffraction. From these simulations, values of the X-ray structure factors for these reflections were deduced, and then used to determine charge difference maps for varioius plane sections in TiAl. These charge difference maps were compared with theoretical predictions, and it was found that there is a considerable degree of agreement between theory and experiment.
Results of Norwood stage I operation: comparison of hypoplastic left heart syndrome with other malformations.

Objective: We compared the Norwood stage I operation for hypoplastic left heart syndrome and other complex malformations with ductus-dependent systemic circulation. Methods: A retrospective study of 194 patients who underwent a Norwood stage I palliation between 1990 and 1998 was conducted. Malformations in 131 patients were classified as hypoplastic left heart syndrome, defined as aortic and mitral atresia or severe stenosis, normal segmental anatomy, intact ventricular septum, and hypoplasia of the left ventricle. Sixtythree patients had other lesions: hypoplastic left ventricle with ventricular septal defect (n = 18), unbalanced complete atrioventricular canal (n = 9), complex double-outlet right ventricle (n = 14), double-inlet left ventricle (n = 11), tricuspid atresia with transposition of the great arteries (n = 6), and others (n = 5), including heterotaxia. Results: Operative (>30 days) and 1-year survivals were lower for patients with hypoplastic left heart syndrome than for those with other lesions (63.4% vs 81%, P = .008, and 51.2% vs 71.4%, P = .02, respectively). The presence of a nonhypoplastic left ventricle (n = 27) was associated with higher operative and 1-year survivals (96.3% vs 64.7%, P = .002; 88.9% vs 52.7%, P < .001). A restrictive atrial septal defect and prematurity tended to increase mortality across both groups. Cox proportional hazards regression indicated that a single right ventricle was the most important independent predictor of death (P < .001). Operative mortality for all patients undergoing the stage I procedure decreased from 38.5% (1990-1994) to 21.4% after 1994 (P = .02). Conclusions: The survival of patients with malformations other than hypoplastic left heart syndrome after the Norwood procedure is greater than for those with hypoplastic left heart syndrome. Staged palliation is valid surgical therapy in these patients, with good results in intermediate follow-up. (J Thorac Cardiovasc Surg 2000; 119:358-67)
The programmable hinge: toward computationally enhanced crafts

Traditionally, the practitioners of home crafting and the practitioners of computing tend to occupy distinct, nonoverlapping cultures. Those small, ubiquitous items of the crafting cultureNstring, thumbtacks, screws, nails, and so forthNthus tend to be viewed as inevitably "lowtech" objects. This paper describes our initial efforts toward integrating computational and crafting media by creating an instance of a computationally-enhanced craft item: a programmable hinge. We describe several prototype models of the hinge; outline a sample project in which the hinge might be employed; and discuss a variety of fundamental issues that affect the design of computationally-enhanced craft items generally.
Genome-Wide Linkage Disequilibrium and Haplotype Maps

There is currently a broad effort to produce genome-wide high-density linkage disequilibrium (LD) maps with single nucleotide polymorphisms. The hope is that the resulting maps can be exploited to find genes that affect the onset and severity of at least some common human diseases. These maps may also be useful for identifying genes that affect drug response or the likelihood of drug toxicities. The goal of this review is to provide a broad overview of some of the key concerns motivating the design of a major international project called the International Haplotype Map Project. The process of map production requires the identification of very large numbers of polymorphic sites, implementation of facile, highly accurate and inexpensive genotyping production pipelines, and provision for public access to the genotype data. Great progress has been made recently in genotyping methods and these advances are allowing very large-scale data collection. A major goal of these efforts is to enable the selection of subsets of markers that capture useful genetic information in short genomic intervals, while optimally reducing the number of markers that must be genotyped. Standard measures of LD provide a starting point but may not fully capture the complexity of the information inherent in the data. Extremely dense genotype data in several broadly representative populations (European, Chinese, Japanese, and Yoruba) should yield important insights into the genetic structure of most genes. Further study is required to determine how broadly applicable the data will be to other population groups. Significant challenges lie ahead in determining the best methods for the selection of markers in disease/phenotype studies, large-scale genotyping, and analysis of the resulting genetic data.
Increased intracellular Ca2+: a critical link in the pathophysiology of sepsis?

Abstract Severe bloodstream-borne infection--i.e., sepsis--and the resulting multiorgan failure are now the most common cause of death in many intensive care units. One of the most fundamentally important and controversial issues concerning the pathophysiology of sepsis is the role of intracellular free calcium concentration ([Ca2+]i) in this disorder. Because of the critical role of calcium as an intracellular second messenger and as a potential cellular toxin, resolution of this issue is crucial. Using 19F NMR spectroscopy and the calcium indicator 5,5'-difluoro-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate we demonstrate in the intact perfused organ, the rat thoracic aorta, that [Ca2+]i in aortic smooth muscle is increased > 2-fold during sepsis. Furthermore, we determined that sodium dantrolene, a drug that decreases release of calcium from the sarcoplasmic reticulum and that is lifesaving in malignant hyperthermia (a disorder due to increased [Ca2+]i), is able to reduce the elevated [Ca2+]i in sepsis to control values when added in vitro or when given in vivo to the animal. These results suggest that an increase in [Ca2+]i is an early event in sepsis and that increased [Ca2+]i may be responsible for, or contribute to, cellular injury. Dantrolene may offer a therapeutic strategy in the treatment of sepsis.
Intrinsic reasoning about functional programs I: first order theories

Abstract We propose a rudimentary formal framework for reasoning about recursion equations over inductively generated data. Our formalism admits all equational programs (including diverging terms), and yet singles out none. While being simple, this framework has numerous extensions and applications. Here we (1) lay out the basic concepts and definitions; (2) show that (for the natural numbers) the deductive power of our formalism is similar to that of Peano's Arithmetic; (3) prove a strong normalization theorem; and (4) exhibit a mapping from natural deduction derivations to an applied λ -calculus, a la Curry–Howard, which provides a transparent proof of Godel's result that the provably recursive functions of PA are definable by primitive recursion in finite types. Also of interest is the extent, uncommon among similar constructions, to which our mapping is oblivious to first order terms, including first order quantification and equality. Additional applications and extensions of the method will be presented in sequel papers. In particular, the methodology introduced here lends itself to systematic links between natural sub-formalisms and computational complexity classes. Since these sub-formalisms are largely transparent, allowing one to reason formally in the full system while leaving to automatic software tools the task of verifying that restrictions are complied with, the framework is particularly attractive for the development of Feasible Mathematics.
Kombinierte Säurekatalyse in der asymmetrischen Synthese durch “Designer‐Säuren”

Lewis- und Bronsted-Sauren konnen durch verfeinerte Techniken in effektivere Reagentien uberfuhrt werden. Ziel der Entwicklung solcher “Designer-Sauren” sind hohe Reaktivitaten und Selektivitaten sowie eine vielseitige Anwendbarkeit bei Reaktionen, die das Potenzial von Saurekatalysatoren nicht vollstandig ausschopfen. In der Katalysatorplanung wird insbesondere das Konzept der kombinierten Sauren zum Design enantioselektiver Katalysen genutzt. Diese sind unterteilt in Bronsted-Saure-aktivierte Lewis-Sauren (BLAs), Lewis-Saure-aktivierte Lewis-Sauren (LLAs), Lewis-Saure-aktivierte Bronsted-Sauren (LBAs) und Bronsted-Saure-aktivierte Bronsted-Sauren (BBAs). Bei der kombinierten Anwendung von Sauren bleibt zum einen die inharente Reaktivitat der assoziierten Komponenten erhalten, zum anderen stehen hoher organisierte Strukturen zur Verfugung, die eine wirksame asymmetrische Umgebung schaffen.
Processing of sun-azimuth information by honey bees

Abstract The dance language of honey bees ( Apis mellifera ) indicates with good accuracy the distance and direction of a food source. When the direction of a food source is moved, however, the dances of returning foragers indicate the former location rather than the new direction just visited. After subsequent trips the dancers slowly accommodate to the change, and full compensation is achieved only after about 40 min. These and other equally curious results suggest that a running-average processing system may be at work in honey bee navigation.
A dominant mutation in mediator of paramutation2, one of three second-largest subunits of a plant-specific RNA polymerase, disrupts multiple siRNA silencing processes.

Paramutation involves homologous sequence communication that leads to meiotically heritable transcriptional silencing. We demonstrate that mop2 (mediator of paramutation2), which alters paramutation at multiple loci, encodes a gene similar to Arabidopsis NRPD2/E2, the second-largest subunit of plant-specific RNA polymerases IV and V. In Arabidopsis, Pol-IV and Pol-V play major roles in RNA–mediated silencing and a single second-largest subunit is shared between Pol-IV and Pol-V. Maize encodes three second-largest subunit genes: all three genes potentially encode full length proteins with highly conserved polymerase domains, and each are expressed in multiple overlapping tissues. The isolation of a recessive paramutation mutation in mop2 from a forward genetic screen suggests limited or no functional redundancy of these three genes. Potential alternative Pol-IV/Pol-V–like complexes could provide maize with a greater diversification of RNA–mediated transcriptional silencing machinery relative to Arabidopsis. Mop2-1 disrupts paramutation at multiple loci when heterozygous, whereas previously silenced alleles are only up-regulated when Mop2-1 is homozygous. The dramatic reduction in b1 tandem repeat siRNAs, but no disruption of silencing in Mop2-1 heterozygotes, suggests the major role for tandem repeat siRNAs is not to maintain silencing. Instead, we hypothesize the tandem repeat siRNAs mediate the establishment of the heritable silent state—a process fully disrupted in Mop2-1 heterozygotes. The dominant Mop2-1 mutation, which has a single nucleotide change in a domain highly conserved among all polymerases (E. coli to eukaryotes), disrupts both siRNA biogenesis (Pol-IV–like) and potentially processes downstream (Pol-V–like). These results suggest either the wild-type protein is a subunit in both complexes or the dominant mutant protein disrupts both complexes. Dominant mutations in the same domain in E. coli RNA polymerase suggest a model for Mop2-1 dominance: complexes containing Mop2-1 subunits are non-functional and compete with wild-type complexes.
Marcus, Kripke, and the origin of the new theory of reference

The New Theory of Reference in the philosophy of language became widespread in the 1970s and is still flourishing today. The New Theory implies that many locutions (e.g., proper names) refer directly to items, which contrasts with the traditional or old theory of reference, which implies that names and relevantly similar locutions express descriptive senses or are disguised descriptions. The New Theory encompasses such notions as direct reference, rigid designation, identity across possible worlds, the necessity of identity, a posteriori necessities, singular propositions, essentialism about natural kinds, the argument from the failure of substitutivity in modal contexts that proper names are not equivalent to contingent definite descriptions, and related ideas and arguments. Some of the contributors to the development of this theory include Kripke, Kaplan, Donnellan, Putnam, Perry, Salmon, Soames, Almog, Wettstein and a number of other contemporary philosophers.
Elevated serum lactate dehydrogenase isoenzymes and aspartate transaminase distinguish Albers-Schönberg disease (Chloride Channel 7 Deficiency Osteopetrosis) among the sclerosing bone disorders.

Osteopetrosis (OPT) refers to the consequences of generalized failure of skeletal resorption during growth. Most cases are explained by loss-of-function mutation within the genes that encode either chloride channel 7 (CLCN7) or a vacuolar proton pump subunit (TCIRG1), each compromising acid secretion by osteoclasts. Patients suffer fractures and sometimes cranial nerve entrapment and insufficient medullary space for hematopoiesis. In 1996, we reported that a high serum level of the brain isoenzyme of creatine kinase (BB-CK), the CK of osteoclasts, characterizes OPT dueamong the sclerosing bone disorders (J Clin Endocrinol Metab. 1996;11:1438). Now, we show that elevation in serum of multiple lactate dehydrogenase (LDH) isoenzymes with aspartate transaminase (AST) distinguishes autosomal dominant OPT due to loss-of-function mutation in CLCN7 [Albers-Schonberg disease (A-SD)] among these conditions. Serum total LDH and AST levels as high as 3× and 2×, respectively, the upper limits of normal for age-appropriate controls, were persistent and essentially concordant in A-SD. Serum LDH was elevated in 7 of 9 children and in the 2 adults studied with A-SD. LDH isoenzyme quantitation showed excesses of LDH-2, -3, and -4. Neither total LDH nor AST increases were found in other forms of OPT, including bisphosphonate-induced OPT, or in 41 children and 6 adults representing 20 additional sclerosing bone disorders. Serum TRACP-5b and BB-CK also were markedly elevated in A-SD. Hence, high serum levels of several enzymes characterize A-SD. Elevated serum LDH isoenzymes and AST indicate a disturbance (of uncertain clinical significance) within multiple extraosseous tissues when there is CLCN7 deficiency.
A Semantic Framework for Translating Web Resources for Endangered Languages: A Yami Language Prototype

This paper describes our attempt at developing web resources for endangered languages. Creating web resources for endangered languages is an important method of developing a language environment for those who speak and those who study the endangered languages. In our study, we propose an approach to creating the web resources for endangered languages. The approach starts with building the ontologies for the endangered languages and creating the mapping to one major language. A framework using the mapping to translate the major language and the endangered language is created. To validate our proposal, we report the process and experiments of creating the web resource translator for translating Yami (an endangered language in Taiwan) to English using the proposed framework.
Ligation of triangles built from bulged 3-arm DNA branched junctions

An important stepping stone to controlled construction on the nanometer scale is the development of rigid components, building blocks whose directions of bonding bear fixed angular relationships to...
Dosimetric consequences of 10B(n,α)7Li reaction occurring at the cellular membrane

Abstract Purpose : Microdosimetric expectations of Boron contents are extracted from a CRAY-Monte Carlo stimulation of the nuclear reaction 10B(n, α)7Li as it occurs on a boronated membrane of a model cell and as the reaction fragments (α and Li) traverse into the cellular nucleus. Methods and Materials : The present microdosimetry calculation is based upon the assumption that the therapeutic advantage of boron neutron capture therapy (BNCT), while depending upon the RBE and LET of the reaction particles, is equally dependent on the boron carrier preferential localization to tumor tissue, and the boron selectivity to cancerous cells and its specificity within the subcellular compartments. In particular, boron fixes to cell membrane as it ought to, using monoclonal antibodies. The present Monte Carlo simulation computes stochastic expectations of α/Li energy depositions to the nucleus in a uniformly boronated membrane shell of a spherical cell. Differential energy gain was deduced from the stochastic energy depositions in events of neutron reactions with membrane boron compared against those with natural elements (O, H, N) in the cell. Results : Microdosimetry data are presented in terms of specific energy ( z keV μ 3 ) and lineal energy (keV/μ) functions of the nucleus-to-cell volume rations (NCVR). When folded with the geometric boron content and accounting for background reaction energies, the distributions yield effective energy gain to the cell nucleus per neutron capture event. Boron amount required to yield these energy gains found to be of the order of picograms of boron per gram of cell mass. Conclusions : The boron content as inferred by the present Monte Carlo microdosimetry compares well with that deliverable by present pharmacokinetic means, but are orders of magnitude (μ-grams) less than those deduced previously from anthropomorphic macrodosimetry.
The Fas apoptotic pathway in cutaneous T-cell lymphomas: Frequent expression of phenotypes associated with resistance to apoptosis

Background Low proliferation rates, sparse apoptotic cells, and resistance to chemotherapeutic agents suggest that defective apoptotic mechanisms may be important in the pathogenesis and progression of cutaneous T-cell lymphomas (CTCLs). Functional studies of CTCL cell lines and leukemic cells further support abnormal expression of Fas apoptotic pathway proteins as a mechanism for resistance to apoptosis. Objective We sought to compare the Fas apoptotic pathway protein expression of mycosis fungoides (MF) with CD30 + lymphoproliferative disorders (CD30 + d) in the context of insights gained from functional studies of CTCL cells. Methods We conducted immunohistochemical analysis of 36 MF and 36 CD30 + d skin biopsy specimens with antibodies against Fas, Fas ligand, FLICE-like inhibitory protein, Fas-associated death domain, and total and cleaved caspases 8 and 3. Results Almost all MF lesions (94%) were Fas ligand–negative. In all, 64% of MF lesions were Fas low. An additional 25% of MF lesions were both Fas high and FLICE-like inhibitory protein high (Fas pathway inhibitor). Altogether, this equated to a phenotype predictive of apoptotic resistance in 89% of MF samples. In 9 of 10 cases of CD30 + d, the apoptotic phenotype predictive of sensitivity/resistance correlated with signs of regression/progression, respectively. Limitations The study is limited by its retrospective design. Discussion Our in situ analysis of MF and CD30 + d tissue samples correlates well with previous functional studies of CTCL cell lines and leukemic blood. Our data strengthen the hypothesis that abnormal expression of upstream Fas pathway factors (Fas, Fas ligand) and the inhibitor FLICE-like inhibitory protein contributes to defective apoptosis in CTCLs.