cssi/SciSciGPT-SciSciNet huggingface dataset:
FDA Approval Summary: Tucatinib for the Treatment of Patients with Advanced or Metastatic HER2-Positive Breast Cancer

On April 17, 2020, the FDA approved tucatinib in combination with trastuzumab and capecitabine for the treatment of patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting. This was the first new molecular entity evaluated under Project Orbis, an FDA Oncology Center of Excellence initiative, which supports concurrent review of oncology drugs by multiple global health authorities. Approval was based on the HER2CLIMB trial, which randomized patients to receive tucatinib or placebo with trastuzumab and capecitabine. Tucatinib demonstrated efficacy compared with placebo in progression-free survival [PFS; HR: 0.54; 95% confidence interval (CI): 0.42-0.71; P < 0.00001] and overall survival (OS; HR: 0.66; 95% CI, 0.50-0.87; P = 0.00480). Patients with either treated and stable or active brain metastases made up 48% of the study population. PFS in patients with brain metastases confirmed benefit (HR: 0.48; 95% CI, 0.34-0.69; P < 0.00001). The benefit in patients with brain metastases allowed for inclusion of this specific population in the indication. Important safety signals included diarrhea and hepatotoxicity which are listed under Warnings and Precautions. This article summarizes the FDA thought process and data supporting the favorable benefit-risk profile and approval of tucatinib.
Development and Evaluation of the Fourier Spectral Distortion Metric

A spatial resolution metric is presented for tomosynthesis. The Fourier spectral distortion metric (FSD) was developed to evaluate specific resolution properties of different imaging techniques for digital tomosynthesis using a star pattern image to plot modulation in the frequency domain. The FSD samples the spatial resolution of a star-pattern image tangentially over an acute angle and for a range of spatial frequencies in a 2D image or 3D image reconstruction slice. The FSD graph portrays all frequencies present in a star pattern quadrant. In addition to the fundamental input frequency of the star pattern, the FSD graph shows spectral leakage, square wave harmonics, and residual noise. The contrast transfer function (CTF) is obtained using the FSD graph. The CTF is analogous to the modulation transfer function (MTF), but it is not normalized to unity at zero spatial frequency. Unlike the MTF, this metric separates the fundamental input-frequency from the other signals in the Fourier domain. This metric helps determine optimal image reconstruction parameters, the in-plane limit of spatial resolution with respect to aliased signals, and a threshold criterion for an image to support super resolution and reduce aliasing artifacts. Various sampling parameters were evaluated to optimize this metric and ascertain measurement accuracy. The FSD adequately compares resolution properties of 2D images and 3D image reconstruction slices for various x ray imaging modes without suppressing aliased signals.
Δ8-THC: Legal Status, Widespread Availability, and Safety Concerns

Delta-8-tetrahydrocannabinol (Δ8-THC) is chemically and functionally similar to delta-9-tetrahydrocannabinol (Δ9-THC) (the primary psychoactive cannabinoid in the cannabis plant) and is currently widely available "over-the-counter" across the United States due to unregulated sales. However, these products have a questionable legal status based on current U.S. laws, as Δ8-THC is considered a Schedule I drug by the federal Drug Enforcement Administration (DEA). Despite this designation, Δ8-THC products (e.g., gummies, edibles, oils, and vapes) are largely unregulated and are sold in gas stations, online, and other marketplaces (most often outside of authorized dispensaries) and are marketed as legal hemp products. This problem arises from a purposeful misinterpretation of the 2018 Farm Bill, which some interpret as legalization of non-Δ9-THC cannabinoids (notably, Δ8-THC). The widespread availability of Δ8-THC products has not been without health consequences. The lack of regulation means that there are no required warning labels or packaging protections in place and no mandated laboratory analysis to assure label accuracy or product purity. As Δ8-THC produces physiological and toxicological effects that are similar to Δ9-THC, high-dose exposure of Δ8-THC (e.g., consuming a full bag of Δ8-THC gummies) has resulted in recent reports of medical emergencies, including calls to poison control centers and presentations to emergency departments, with some pediatric patients arriving unconscious and unresponsive. Several states and regulatory agencies have called for legislation to regulate Δ8-THC, but little progress has occurred nationally thus far.
Information and the Limits of Unlimited Supply

It is sometimes thought that that legal protection of intellectual property is illegitimate because the supply of information objects is “unlimited.” On this view, there can be no rational point to recognizing and protecting property rights in an object that is available in unlimited supply; the costs of enforcement, one might argue, results in no significant benefit because it makes no sense to protect a person’s right to exclude others from consuming an object that is available in infinite supply. In this essay, I raise some questions about what can properly be inferred from the claim that the supply of information objects is “unlimited” in the relevant sense.
German Histories in the Age of Reformations, 1400–1650

Part I. The Empire and the German Lands: 1. Reformations in German histories 2. Shapes of the German lands 3. Temporal estates - farmers, traders, fighters 4. The church and the faith Part II. Reform of Empire and Church, 1400-1520: 5. Reform of empire and church 6. The empire and the territorial states 7. The reform of the empire in the age of Maximilian 8. Ideals and illusions of reforming the church Part III. Church, Reformations, and Empire, 1520-76: 9. Urban reformations 10. Revolution of the common man 11. Imperial reformations in the age of Charles V 12. Imperial peace, 1555-80 Part IV. Confessions, Empire, and War, 1576-1650: 13. Forming the Protestant confessions 14. Reforming the Catholic church 15. Limits of public life - Jews, heretics, witches 16. Roads to war 17. The Thirty Years War 18. German reformations, German futures.
Crystallographic analysis of trypsin-G226A. A specificity pocket mutant of rat trypsin with altered binding and catalysis.

The crystal structure of trypsin-G226A has been determined, in the presence of benzamidine, to a resolution of 1.75 A with an R-factor of 14.6%. The mutation was designed to alter substrate specificity by disrupting arginine binding, but was previously found to disrupt catalysis to a greater extent, than binding. The arginine analog, benzamidine, has rotated 40 ° and 49 ° and translated 1.1 A in the specificity pocket, relative to the position in wild-type trypsin. The salt-bridge between the amidinium group of benzamidine and the carboxylate of D189 as well as four other hydrogen bonds have been replaced by a set of six new hydrogen bonds. Based on these interactions, computer modeling of an arginine substrate demonstrates that arginine terminal nitrogen atoms can occupy the new benzamidine nitrogen positions with torsion angle adjustments and without short contacts. In the secondary orientation, arginine substrates appear to be forced out of alignment with the active site. This may account for the larger drop in kcat with arginine relative to lysine substrates. A second possible cause of the altered activity is a change of the enzyme structure with concomitant loss of activity. No evidence of such a change is seen in the co-ordinates or temperature factors of the trypsin-G226A-benzamidine complex. A226 disrupts mainly the co-ordinates of amino acids with which it has direct contacts such that the effects of the mutation are absorbed locally.
Techniques for Non-Birefringent Objects: Coherent Shearing Interferometry and Caustics

Shearing interferometric techniques that can provide information about the stress or deformation states of non-birefringent transparent materials and opaque specularly reflective materials are described. Two types of coherent shearing interferometers that provide full-field information about the gradients of the stress state of an object are discussed. These techniques have recently found use in stress analysis, especially in experimental fracture mechanics studies. In addition, a simpler technique called the method of caustics which is also applicable to non-birefringent materials is described in brief. This technique does not provide full-field information but has been of historical interest in experimental fracture mechanics. Examples of application of all three techniques are given.
The Ivory Tower in a Flat World the University and Applied Sociology in the Global Economy

This paper focuses on the image and the role of higher education and the university in an increasingly globalized context. The recent popular book by Thomas Friedman, The World Is Flat, provides an...
Novel Three-Dimensional Electrodes: Electrochemical Properties of Carbon Nanotube Ensembles

We report on the electrochemical study of three carbon nanotube ensemble electrodes: single-walled nanotube paper, as-produced multiwalled nanotube towers, and heat-treated multiwalled nanotube towers. Cyclic voltammetry was used in 0.10 M KCl containing 5.0 mM K4Fe(CN)6 to obtain information on both the capacitive background and electron transfer rate from the faradaic reaction of the redox species. The capacitance gives insight into the effective surface area (including both the exterior surface and the interior surface within the film) as well as the “pseudocapacitance” due to faradaic reactions of surface bonded oxides. We found that a large portion of the carbon nanotube surface of the as-produced multiwalled nanotube tower electrode was blocked by amorphous carbon. It can be largely removed by prolonged heat treatment. Among the three types of samples, the single-walled nanotube paper electrode presented the largest volume specific capacitance, consistent with its highest carbon nanotube packing de...
Public administrators and policy legitimization: Policy analysis, politics and power

This article discusses the factors public administration faculty should incorporate into the curriculum in order to equip students to engage in the policy legitimization process. In order to produce leaders, public administration programs should emphasize the nature of the political system, an understanding of the legitimacy of subgovernments, the importance of coalition building and the psychological factors associated with policy choices. Integration of policy analysis into the public administration curriculum requires that students be equipped with an in-depth understanding of both the political environment and the political process. This is true because public administrators are deeply involved in the stages of policy development, adoption, and implementation; activities which reach beyond the narrow confines of program management and into the realm of politics. Consequently, public administrators serve in a variety of capacities: as policy advocates, program champions, or as defenders of client inter...
Experimental autoimmune encephalomyelitis as a testing paradigm for adjuvants and vaccines

Experimental autoimmune encephalomyelitis (EAE) is an experimental model for multiple sclerosis. EAE can be induced by inoculation with central nervous system (CNS) proteins or peptides emulsified in complete Freund's adjuvant. Protection from EAE, enhancement of EAE or subclinical priming for EAE can occur as a result of either live viral infection or DNA immunization with molecular mimics of CNS proteins or peptides. Here we review the published data describing modulation of EAE through administration of various CNS proteins/peptides introduced via live virus or plasmid DNA and modulation of EAE through choice of adjuvant (immunostimulating agents).
Deposition and Characterization of Extended Single-Stranded DNA Molecules on Surfaces

We have devised an approach for generating well-extended, surface deposited, single-stranded DNA molecules having minimal intramolecular base-pairing. This method depends on careful control of the mica surface charge, appropriate selection of the ionic strength of the DNA solution, and controlled translation of a droplet of DNA solution along the surface. We have shown the general applicability of this technique by elongating ΦX174, M13mp18, and λ single-stranded DNA on mica followed by imaging with atomic force microscopy. We have further demonstrated the feasibility of more elaborate, multistep surface preparations by aligning λ double-stranded DNA and ΦX174 single-stranded DNA in orthogonal directions on the same substrate.
The Laser-Mössbauer Method for Surface Evolution and Thin Film Microstructure

Using amorphous Fe81B13.5Si3.5C2, Fe40Ni38Mo4B18, Fe66Co18B15Si1 and Fe72.6Cr22Al4.8Si0.3Y0.3 as model systems, we apply the laser-Mossbauer method in order to obtain metallic glasses with novel properties. As shown by transmission Mossbauer spectroscopy, the bulk magnetic texture was modified in a rational manner by applying a varying number of excimer laser pulses per spot (λ=248 nm, τ=8 ns). As shown by conversion electron Mossbauer spectroscopy, this process left the surface magnetic texture unchanged and induced a distribution of magnetic moment directions throughout the thickness of the foil. A similar dependence of the magnetic texture upon the number of applied laser pulses was obtained in metallic glasses irradiated with a Nd:YAG laser (λ=532 nm, τ=8 ns). However, in this case we observed the onset of surface crystallization in the hyperfine magnetic field distributions extracted from the CEMS spectra. When a pulsed alexandrite laser was used (λ=750 nm, τ=60 μs), the onset of crystallization was found to be accompanied by bulk oxidation and the formation of magnetite particles in the irradiated system. Finally, a crucial experiment was performed in order to demonstrate the role played by the magnetostriction constant in the onset of crystallization.
Engineering the perfect (bacterial) cancer therapy

Bacterial therapies possess many unique mechanisms for treating cancer that are unachievable with standard methods. Bacteria can specifically target tumors, actively penetrate tissue, are easily detected and can controllably induce cytotoxicity. Over that last decade, Salmonella, Clostridium and other genera have been shown to control tumor growth and promote survival in animal models. In this Innovation article I propose that synthetic biology techniques can be used to solve many of the key challenges associated with bacterial therapies such as toxicity, stability and efficiency; and can be used to tune their beneficial features, allowing the engineering of ‘perfect’ cancer therapies.
Inhaled Corticosteroids and Bone Density

We also previously published our data in an abstract.3 We do not have a good explanation as to why the pneumothorax rate is so variable among different clinical series. We thought that our rate of 35.4% was high but there are reported rates as high as 60%. Patient and lesion selection may be at least as important as technical and operator-related factors. As an example, one clinical series using sonographic guidance had 5 of 124 patients (4.0%)4 with pneumothorax. Such a low rate may be expected in lesions capable of being imaged by ultrasound, which are usually adjacent to solid structures.
Structural Depth Profiling by Glancing Angle X-ray Diffraction

Presented here is a technique to structurally depth profile multilayer films using a Seemann-Bohlin triple axis x-ray diffractometer and a 12 kW rotation anode x-ray source. This paper discusses the Seemann-Bohlin geometry and aberrations related to depth profiling and refraction. The technique was successfully applied to multilayer metallic-thin films a few hundred angstroms thick and demonstrated to have an excellent sensitivity to ultra thin-metallic films less than 25 angstroms thick.
Dry Machining Using Vortex-Tube Generated Cold Air as Coolant: A Literature Review

This paper reviews the literature on dry machining with VT cooling (using vortex-tube generated cold air as coolant). It presents reported experimental results on effects of VT cooling on cutting force, cutting temperature, tool wear, surface roughness, and residual stress. It also points out areas where VT cooling applications have not been reported and potential directions for future research.Copyright © 2008 by ASME
An Instrument for Exposing Host Insects to Parasites

Studies to develop in vitro rearing systems for parasitic insects require a daily supply of parasite eggs (0–4 h old) which are dissected from natural host eggs. An instrument was designed, tested, and used to expose host insects automatically to parasites when activated by a present timer. Host and parasite were confined in separate chambers in this device at the end of each workday and the timer set to pull a partition from between the chambers 4 h before the start of the next workday. This device was in daily operation for more than a year without a failure and provided 0-to-4-h-old parasite eggs for use in our studies at the start of each workday with a savings of ca. 4 h/day.
A pressure vessel fracture mechanics study of the aluminum beverage can

Abstract Two fracture mechanics studies were conducted using two different aluminum beverage containers (wall thicknesses of 0.0044 in. [0.112 mm] and 0.0039 in. [0.099 mm]). The first study involved a 1.25 in. (31.75 mm) wide center-cracked panel specimen to measure the axial fracture resistance of the containers. Factors contributing to beverage container fracture resistance are discussed, including the thickness and rolling direction orientation. Due to the extremely thin nature of these containers, a reduced specimen thickness leads to a reduced fracture resistance. This resistance is also seen to increase as the orientation to the material rolling direction becomes perpendicular. The second study was a full-scale, leak-before-break rupture test. Each container had a crack of a known length and depth machined in the exterior wall. The stress intensity factor of these cracks upon failure gives excellent correlation to the center-cracked panel specimens as well as to other models for predicting pressure vessel rupture.
Neural Activity in Macaque Parietal Cortex Reflects Temporal Integration of Visual Motion Signals during Perceptual Decision Making

Decision-making often requires the accumulation and maintenance of evidence over time. Although the neural signals underlying sensory processing have been studied extensively, little is known about how the brain accrues and holds these sensory signals to guide later actions. Previous work has suggested that neural activity in the lateral intraparietal area (LIP) of the monkey brain reflects the formation of perceptual decisions in a random dot direction-discrimination task in which monkeys communicate their decisions with eye-movement responses. We tested the hypothesis that decision-related neural activity in LIP represents the time integral of the momentary motion "evidence." By briefly perturbing the strength of the visual motion stimulus during the formation of perceptual decisions, we tested whether this LIP activity reflected a persistent, integrated "memory" of these brief sensory events. We found that the responses of LIP neurons reflected substantial temporal integration. Brief pulses had persistent effects on both the monkeys' choices and the responses of neurons in LIP, lasting up to 800 ms after appearance. These results demonstrate that LIP is involved in neural time integration underlying the accumulation of evidence in this task. Additional analyses suggest that decision-related LIP responses, as well as behavioral choices and reaction times, can be explained by near-perfect time integration that stops when a criterion amount of evidence has been accumulated. Temporal integration may be a fundamental computation underlying higher cognitive functions that are dissociated from immediate sensory inputs or motor outputs.
Bladder control, urgency, and urge incontinence: Evidence from functional brain imaging

Aim To review brain imaging studies of bladder control in subjects with normal control and urge incontinence; to define a simple model of supraspinal bladder control; and to propose a neural correlate of urgency and possible origins of urge incontinence. Methods Review of published reports of brain imaging relevant to urine storage, and secondary analyses of our own recent observations. Results In a simple model of normal urine storage, bladder and urethral afferents received in the periaqueductal gray (PAG) are mapped in the insula, forming the basis of sensation; the anterior cingulate gyrus (ACG) provides monitoring and control; the prefrontal cortex makes voiding decisions. The net result, as the bladder fills, is inhibition of the pontine micturition center (PMC) and of voiding, together with gradual increase in insular response, corresponding to increasing desire to void. In urge-incontinent subjects, brain responses differ. At large bladder volumes and strong sensation, but without detrusor overactivity (DO), most cortical responses become exaggerated, especially in ACG. This may be both a learned reaction to previous incontinence episodes and the neural correlate of urgency. The neural signature of DO itself seems to be prefrontal deactivation. Possible causes of urge incontinence include dysfunction of prefrontal cortex or limbic system, suggested by weak responses and/or deactivation, as well as abnormal afferent signals or re-emergence of infantile reflexes. Conclusions Bladder control depends on an extensive network of brain regions. Dysfunction in various parts may contribute to urge incontinence, suggesting that there are different phenotypes requiring different treatments. Neurourol. Urodynam. 27:466–474, 2008. © 2007 Wiley-Liss, Inc.
Two-Level Minimally Invasive Transforaminal Lumbar Interbody Fusion: Surgical Technique and Illustrative Cases

Transforaminal lumbar interbody fusion (TLIF) is a common procedure performed by spine surgeons. The indications for TLIF include back pain and radiculopathy as a consequence of canal or foraminal stenosis, degenerative disc disease, spondylolisthesis, or deformity. Minimally invasive techniques (MIS) have proven to be effective for single-level TLIF and are associated with less blood loss, fewer wound complications and infections, faster recovery, and decreased hospital cost. To date, there is very little data on 2-level MIS TLIF. We present our technique for 2-level MIS TLIF with case illustrations and a review of the literature.
Retrievals of thin cloud optical depth from a multifilter rotating shadowband radiometer

[1] A method is developed for accurate retrieval of thin cloud optical depth from measurements of a multifilter rotating shadowband radiometer (MFRSR). A key feature of this technique is correction of strong forward scattering of solar radiation into the instrument's field of view, which causes underestimation of retrieved cloud optical depth. To develop the correction method, measurements from the MFRSR under various atmospheric conditions are simulated by using a modified DISORT code that can accurately compute radiative intensity for strong forward scattering by thin clouds. These simulations are used to develop a polynomial fitting technique that corrects forward scattering into direct beam component. The correction is then applied to real MFRSR measurements. First, temporal and spectral variations in direct beam observations are used to discriminate between aerosol and thin cloud conditions. The true thin cloud optical depth, then, is inferred by removing background aerosol optical depth and by applying the polynomial fitting technique to correct the forward scattering contribution. An analysis of uncertainties associated with this method is also conducted and the results show that the retrievals are accurate to better than 5% or 0.05 when optical depth is less than 1.
L1 effects on the emergence of ESL sentence processing skills of Chinese and Korean ESL learners: A preliminary study

This study examines the emergence of lower-level ESL sentence processing skills involved in integrating English words into predicate structures on-line. The aim of the present study is to examine how the L1 phrase structure and corresponding L1 word integration skills of ESL learners influence their corresponding ESL sentence processing skills in an on-line English sentence reading task. The study examined the English predicate and verb phrase processing skills of a group of Chinese ESL learners whose language has right-branching L1 verb phrase structures (head-complement word order) and a group of proficiency-matched Korean ESL learners whose native language only allows left-branching L1 verb phrase structures (i.e., complement-head word order). The Chinese ESL group (n = 20) was significantly faster than the Korean ESL group (n = 18) in reading and integrating direct object nouns into English predicate phrase structures, though there were no significant differences comprehending the sentences. In addition, the Chinese ESL group was significantly more accurate in reading and comprehending transitive sentences in which the direct objects had an embedded relative clause. The results suggest that L1 word integration skills influence and shape the emergence of on-line ESL word integration
Earthquake impact in a remote South Asian population: Psychosocial factors and posttraumatic symptoms

Although previous studies have documented the psychological impact of earthquakes, less is known about potentially protective characteristics associated with healthier outcomes. In the present study, 2 samples of survivors were recruited from remote villages in Northwestern Pakistan, 7 and 19 months after the devastating October 2005 earthquake. Female gender, lower education, and closer proximity to the epicenter predicted significantly higher posttraumatic symptom levels. After adjusting for demographic characteristics, distance from the epicenter, and death of close relatives, higher dispositional optimism and higher scores on the Connor-Davidson Resilience Scale were significantly associated with lower symptom levels. The authors' findings in a previously unstudied population suggest that certain potentially protective mechanisms, such as optimism, may be universal regardless of culture of origin.
Discourse ethics and the political conception of human rights

This article examines two recent alternatives to the traditional conception of human rights as natural rights: the account of human rights found in discourse ethics and the ‘political conception’ of human rights influenced by the work of Rawls. I argue that both accounts have distinct merits and that they are not as opposed to one another as is sometimes supposed. At the same time, the discourse ethics account must confront a deep ambiguity in its own approach: are rights derived in a strong sense from the conditions of ‘communicative freedom’ or are they developed from the participants’ own reflection upon their ongoing and continuously changing practices and institutions? The political conception recently proposed by Joshua Cohen can, I argue, contribute to the resolution of this ambiguity, though not without some modifications of its own. Keywords: human rights; discourse ethics; The ‘political conception’ of rights; Seyla Benhabib; John Rawls; Rainer Forst; Michael Ignatieff; Thomas Pogge; Joshua Cohen (Published: 10 March 2009) Citation: Ethics & Global Politics. DOI: 10.3402/egp.v2i1.1938
New relativistic generalization of the Heisenberg commutation relations

A relativistic generalization of the Heisenberg commutation relations is suggested which is different from the conventional ones used for the intrinsic coordinates and momenta in the relativistic oscillator model and the relativistic string. This new quantum relativistic oscillator model is determined by the requirement that it gives a unified description of relativistic vibrations and rotations and contracts in the nonrelativistic limit ${c}^{\ensuremath{-}1}\ensuremath{\rightarrow}0$ into the usual nonrelativistic harmonic oscillator.
Fragments of filamentous phage f1: cellular fate of the DNA.

Abstract The intracellular fate of the DNA of active f1 fragments created by sonic irradiation of whole f1 has been studied. Sedimentation analysis of the DNA segments which enter the male cell indicates them to be very small (perhaps only a few hundred nucleotides in length). The extracted DNA is a good substrate for Escherichia coli exonuclease I and bands in CsCl density gradient centrifugation with single-stranded f1 DNA. The DNA fragments extracted from the cells appeared to be approximately two-thirds the size of input fragment DNA. These results imply that the viral DNA fragments persist as single-stranded, linear polynucleotides in vivo and may be partially degraded.
A proteolytic pathway that controls glucose uptake in fat and muscle.

Insulin regulates glucose uptake by controlling the subcellular location of GLUT4 glucose transporters. GLUT4 is sequestered within fat and muscle cells during low-insulin states, and is translocated to the cell surface upon insulin stimulation. The TUG protein is a functional tether that sequesters GLUT4 at the Golgi matrix. To stimulate glucose uptake, insulin triggers TUG endoproteolytic cleavage. Cleavage accounts for a large proportion of the acute effect of insulin to mobilize GLUT4 to the cell surface. During ongoing insulin exposure, endocytosed GLUT4 recycles to the plasma membrane directly from endosomes, and bypasses a TUG-regulated trafficking step. Insulin acts through the TC10α GTPase and its effector protein, PIST, to stimulate TUG cleavage. This action is coordinated with insulin signals through AS160/Tbc1D4 and Tbc1D1 to modulate Rab GTPases, and with other signals to direct overall GLUT4 targeting. Data support the idea that the N-terminal TUG cleavage product, TUGUL, functions as a novel ubiquitin-like protein modifier to facilitate GLUT4 movement to the cell surface. The C-terminal TUG cleavage product is extracted from the Golgi matrix, which vacates an “anchoring” site to permit subsequent cycles of GLUT4 retention and release. Together, GLUT4 vesicle translocation and TUG cleavage may coordinate glucose uptake with physiologic effects of other proteins present in the GLUT4-containing vesicles, and with potential additional effects of the TUG C-terminal product. Understanding this TUG pathway for GLUT4 retention and release will shed light on the regulation of glucose uptake and the pathogenesis of type 2 diabetes.
Independent analysis of Olympus flexible ureteroscope repairs.

OBJECTIVES To conduct a systematic review of repairs of Olympus flexible ureteroscopes using an independent database to compare and contrast with the published data obtained from ureteroscope manufacturers. METHODS The repair data from 2000 to 2004 were extracted from a computer database obtained through Precision Endoscopy of America, an independent endoscope repair company. All endoscopes submitted for repair underwent a detailed 16 to 32-point inspection using a set protocol for each endoscope make and model, as determined by the manufacturer. RESULTS A total of 341 repairs were performed on the Olympus URF-P (4%), URF-P2 (47%), and URF-P3 (47%) flexible ureteroscopes. The distal segment was the most common repair site requiring repair (30%), with 87% of these repairs requiring replacement of the bending rubber. The repairs also included the deflection apparatus (14%) and hand control segment (9%) and image-related repairs (9%). The between-group assessment showed a statistically significant decrease in deflection apparatus repairs for the URF-P2 (20%) compared with the URF-P3 (7%; P <0.001, chi-square = 11.96). CONCLUSIONS The results of our study have shown that the loss of deflection is less common with the newer Olympus ureteroscopes. The distal deflection tip, specifically the outer bending rubber, is the most common site of damage to Olympus flexible ureteroscopes. Improvements in form and function of the distal tip should decrease the maintenance expenses and increase ureteroscope longevity.
The California ice-age refugium and the Rancholabrean extinction problem

The question of what caused the late Quaternary extinction of the Rancholabrean fauna in the California glacial refugium is examined. In the absence of significant climatic and other natural environmental change, man was probably the principal agent of extinction in California. This extinction event marked the beginning of a long history of environmental impact in the area by humans.
Integrated semigroups, C-semigroups and the abstract Cauchy problem

LetA be a linear operator on a Banach space. We consider when the following holds. (*)u′(t,x)=A(u(t,x)) (t≥0),u(0,x)=x, has a unique solution, for allx in the domain ofA n+1 .
Characterizing Key Developmental Understandings and Pedagogically Powerful Ideas Within a Statistical Knowledge for Teaching Framework

A hypothetical framework to characterize statistical knowledge for teaching (SKT) is described. Empirical grounding for the framework is provided by artifacts from an undergraduate course for prospective teachers that concentrated on the development of SKT. The theoretical notion of “key developmental understanding” (KDU) is used to identify landmarks in the development of SKT subject matter knowledge. Sample KDUs are given for the subject matter knowledge categories of common content knowledge, specialized content knowledge, and horizon knowledge. The theoretical notion of “pedagogically powerful idea” is used to describe how KDUs must be transformed to become useful in teaching. Examples of pedagogically powerful ideas for the pedagogical content knowledge categories of knowledge of content and teaching and curriculum knowledge are provided. Knowledge of content and students is hypothesized as a basis for the development of pedagogically powerful ideas.
1449 ANTHROPOMETRIC CORRELATES OF CREATININE EXCRETION IN PREMATURE INFANTS

Urinary creatinine excretion has been utilized to assess malnutrition, prorate the excretion of urinary metabolites and measure renal function. Creatinine output (mg per kg body weight) increases throughout childhood. There are no data describing the anthropometric correlates of creatinine excretion in the premature infant. Accordingly,we measured urinary creatinine output in timed 24-hour urine specimens obtained in the second week of life on 15 premature infants (mean weight 1.21kg, range 0.760 to kg; mean gestational age 29 weeks, range 26 to 33 weeks). The following regression equations were obtained: Stepwise regression yielded no linear combination of these variables that improved the estimate based on weight alone. In a similar manner, consideration of weight and length for age (expressed as percent of 50th percentile) did not improve the estimate based on weight alone. These data demonstrate that creatinine output in mg per kg increases by 15% between 0.7 and 1.5 kg birthweight. This increase parallels that in body protein content per kg obtained from published fetal body composition data in similarly aged infants. Creatinine output in premature infants therefore can serve as a reflection of growth of lean body mass.
Note on a class of alternatives for the equal probabilitiesX 2 test

Some properties of a class of alternatives to the hypothesis of equal probabilities in theX2 goodness-of-fit test are studied. The resulting limiting distribution and power function are discussed. A regression test is also considered.
Distamycin A-DAPI banding of nonfluorescent Y(Ynf) chromosomes in 45,X/46,XYnf mosaicism.

The distamycin A-DAPI banding patterns of nonfluorescent, nonheterochromatic Y chromosomes (Ynf) in two patients with 45,X/46,XYnf mosaicism were investigated. In both cases moderately fluorescent bands were observed near the centromere and on the distal long arm of the Ynf. These bands were similar to the centrometric band on normal Y chromosomes and support the hypothesis that the Ynf is an isodicentric chromosome derived from the proximal portion of the Y chromosome.
Developing teaching knowledge through peer discourse

Abstract The central focus of the research reported here was to evaluate the usefulness of peer interaction on the development of professional knowledge of prospective secondary mathematics teachers. Tracing the fate of two students involved in a teamed field-based practicum experience over the course of 11 weeks, the findings of the research indicate that the use of peer collaboration and collaborative reflection has the potential to facilitate teacher development. Peers helped problematize learning issues, teaching actions, and mathematics for one another. Their level of reflection increased in the process.
Student-Designed Multistep Synthesis Projects in Organic Chemistry

The incorporation of research projects into undergraduate chemistry courses provides a perspective that is fundamentally unavailable in most laboratory experiences. While independent, multistep synthesis projects in organic chemistry have been reported previously, most efforts have been directed at relatively restricted, closely guided research plans with modest student participation in the experimental design. We have implemented a more open-ended synthesis project, limited principally by cost, safety and availability of materials. In the second semester of the sophomore organic sequence, students develop multiple drafts of a plan for a three-to-four-step synthesis. Subsequently, students obtain their own literature protocols for the individual steps. The synthesis is performed over three four-hour laboratory periods. The students conclude this project with a poster presentation of the results at the end of the semester. Evaluation of the students’ work focuses not only on the successful synthesis of the target but also on planning, troubleshooting, purification, and spectral analysis.
On the space group of La2CuO4−δ

Abstract The space groups of orthorhombic La2CuO4−δ and related superconducting perovskites have variously been reported as Fmmm, Abma, Bmab, Cmca, Fmm2, Cmmm, Pccm and Pccn. The lack of a universal convention for the selection of the a, b and c axes in orthorhombic structures has added to the confusion. The presence of transformation twins in the microstructure is a possible cause of some of the erroneous determinations. In this paper we review the different space groups suggested in the literature along with the choice of axes. We also present electron diffraction data obtained from single-crystal La2CuO4−δ and a discussion of the conditions limiting possible reflections which help to distinguish between the various possible space groups. We conclude that the space group is Bmab based on a unit cell with lattice parameters a0
MOTIVATIONAL CHANGES IN THE RAT FOLLOWING LESIONS OF THE MESENCEPHALIC RETICULAR FORMATION.

Abstract Tegmental lesions produced high as well as low terminal response rates in rats trained on a fixed-interval reinforcement schedule. This diversity of effect on a measure reflecting motivational or drive level points to the complexity of reticular influence on mechanisms of motivation and suggests that this influence is the resultant of mutually opposing processes. Finally, none of the lesions including those restricted to the red nucleus impaired temporal discrimination.
Zero-temperature attenuation and transverse spin dynamics in fermi liquids. III. Low spin polarizations

This is the third in a series of papers on microscopic theory of transverse dynamics in spin-polarized Fermi liquids. In the lowest order in polarization our exact general theory of Ref. 1 reproduces the conventional Landau-Silin-Leggett theory of Fermi liquids. The next term in polarization expansion contains a zero-temperature attenuation with the magnitude that does not depend on polarization. This attenuation results in a finite relaxation time in transverse spin dynamics at zero temperature and is responsible for anomalous temperature behavior of spin diffusion. The zero-temperature attenuation is determined by two angular harmonics of the derivatives of the mass operators and the irreducible vertex in off-shell directions, and cannot be expressed via standard Fermi liquid harmonics. At high polarizations, the parameters of transverse spin dynamics are calculated as an expansion in polarization. The expansion involves complex values of interaction function and energy on a set of isoenergetic surfaces with the radii between the Fermi momenta for up and down spins,p↓ andp↑. The results explain recent experimental data on spin diffusion in spin-polarized liquid3He↑ and3He↑-4He mixtures. The comparison with experimental data indicates that the superfluid transition temperature for3He in3He-4He mixtures may be much lower than the current estimates.
Deadlock-avoidance control of multithreaded software: An efficient siphon-based algorithm for Gadara petri nets

This paper presents an efficient implementation of an iterative control algorithm for the synthesis of maximally-permissive liveness-enforcing control policies for Gadara nets presented in earlier work. Gadara nets are a special class of Petri nets arising when modeling multithreaded software for the purpose of deadlock analysis and resolution. The considered control synthesis algorithm is based on structural analysis of Gadara nets in terms of a certain type of siphons, called resource-induced deadly-marked siphons. We propose a new customized mixed integer programming formulation to detect these siphons in Gadara nets. We then compare the performance of our customized algorithm with that of a generic siphon detection algorithm for process-resource nets in the context of the iterative control algorithm. Finally, we investigate the scalability of the overall algorithm to large program models.
Long-term seizure control outcomes after resection of gangliogliomas.

Background Gangliogliomas are rare glioneuronal tumors that typically cause refractory seizures during the first 3 decades of life. Objective To determine the prognosticators of seizure outcome after surgery for ganglioglioma. Methods We reviewed the cases of 66 patients who underwent resection of gangliogliomas at the University of California, San Francisco. Demographic, seizure history, and operative data were examined for statistical association with postoperative seizure outcomes. Results Of the 66 patients who underwent surgical resection of ganglioglioma, 49 patients (74%) presented with a history of seizures. Of those 49 patients, 50% presented with intractable epilepsy. Temporal lobe gangliogliomas were present in 76% of the patients who presented with a history of seizures. Electrocorticography was performed on 35% of the patients, and of those patients, 82% underwent extended lesionectomy to remove abnormally epileptogenic extralesional tissue. The median follow-up duration was 6.9 years, during which tumor progression occurred in 38% of patients who underwent subtotal resection and in 8% of patients who underwent gross total resection (P = .02). Overall, 85% of patients were seizure free (International League Against Epilepsy class I or II) 5 years after surgery. Subtotal resection was associated with poor seizure outcomes 1 year after resection (odds ratio = 14.6; 95% confidence interval = 2.4-87.7): rates of seizure freedom were 54% after subtotal resection, 96% after gross total resection, and 93% after gross total resection with intraoperative electrocorticography-guided extended lesionectomy. Conclusion We report excellent long-term seizure control outcomes after surgery for gangliogliomas. Intraoperative electrocorticography may be a useful adjunct for guiding extended resection in certain pharmacoresistant epilepsy patients with gangliogliomas. Subtotal resection is associated with higher rates of tumor progression and nonoptimal seizure outcomes.
Oral Exposure of PBDE-47 in Fish: Toxicokinetics and Reproductive Effects in Japanese Medaka (Oryzias latipes) and Fathead Minnows (Pimephales promelas)

The toxicokinetics of 2,2,4,4-tetrabromodiphenyl ether (PBDE-47) was studied in the Japanese Medaka (Oryzias latipes) after a single oral exposure followed by termination at specific time points. The effects of repeated oral exposure to PBDE-47 on reproductive performance was assessed using a pair breeding experimental design with fathead minnows (Pimephales promelas) given daily PBDE-47 exposures for 25 days, during which fecundity was measured as an indicator of reproductive performance. Medaka and fathead minnows were orally exposed to PBDE-47 by bioencapsulation in brine shrimp, Artemia sp. In the medaka studies, measurable levels of PBDE-47 were detected in the carcass within 0.25 h with peak levels occurring at 8 h. The body levels of PBDE-47 slowly declined and were still 25% of peak levels at 624 h after dosing. Assimilation of the bioencapsulated dose was at least 80% and may well approach 100%. The PBDE-47 concentration-time profile was fitted to a one-compartment clearance-volume toxicokinetic model and the model-predicted value for elimination half-life was determined to be 281 h and the first-order absorption rate constant was Ka = 0.26 hr(-1). In the fathead minnow study, egg laying in the PBDE-treated breeding pairs stopped after 10 days. The condition factor of PBDE-treated males was significantly reduced (P <0.011) compared with control males, whereas no significant difference was observed in females. Histological examination revealed a greater than 50% reduction in mature sperm in PBDE-47 exposed minnows compared to controls. Collectively, these results suggest PBDE-47 is selectively toxic to sexually mature male fathead minnows.
A Zener diode model for computer circuit simulations

A Zoner diode equivalent circuit suitable far CAD programmes and containing no sources is developed that models the large-signal V-I Zener curve, temperature coefficient of Zener voltage, and small signal resistance.
Using UNIACT in a Comprehensive Approach to Assessment for Career Planning.

The Unisex Edition of the ACT Interest Inventory (UNIACT; Swaney, 1995) is the chief component of a comprehensive, integrated approach to assessment for career planning and replanning. The World-of...
Exact-finite-range DWBA calculations of massive transfer reactions treated as breakup-fusion reactions

Abstract Distorted-wave-Born-approximation calculations, with the exact-finite-range method, were performed, and good fits were obtained to data of the α singles cross sections in the 181 Ta ( 14 N , α) reaction, taken as an example. It is shown that the breakup-fusion is not a simple peripheral process, but takes place in a region which is about 2 fm deeper than is the usual peripheral region.
Eye Movements Recorded During Convergence and Divergence

The purpose of the present experiments was to record horizontal binocular eye movements during normal amounts of convergence and divergence by a method having satisfactory sensitivity and accuracy. This is a method of direct photography, based upon collimated beams of light reflected from plane mirrors mounted on tightly fitting contact lenses. The records show that the eyes exhibit relatively rapid and accurate motions of vergence when fixating alternately a near and a far test object. There is no evidence for a systematic discrepancy between the extent of vergence and the geometrical location of the test object. It is concluded that when fusion is maintained, the images of a fixation object are brought to corresponding areas of the retina to an accuracy of about two minutes of arc. This finding is consistent with the reported sizes of Panum’s area and the region of optimal visual resolution.