cssi/SciSciGPT-SciSciNet huggingface dataset:
Genetic Defects in SHROOM3 Lead to Congenital Heart Defects

Background and Hypothesis: Congenital heart disease(CHD) is the most common birth defect, but most genetic contributors remain unknown. We recently identified CHD patients with variants in a gene called SHROOM3. The SHROOM3 protein impacts the actin cytoskeleton by binding ActinF and Rho-kinase, causing actomyosin constriction. SHROOM3 also binds Dishevelled2(Dvl2), a component of Wnt/Planar cell polarity(PCP) signaling pathway, suggesting a connection between PCP signaling and actin-myosin contraction. We hypothesize SHROOM3 disruption alters PCP signaling and actin cytoskeleton during cardiac development, and is a novel contributor to CHD. Project Methods: We analyzed the cardiac phenotype of Shroom3 gene trap knockout mice at embryonic day 14.5. We characterized the expression of Shroom3 during cardiac development using LacZ staining at important stages of cardiac development. Using IHC, we measured actomyosin disruption in Shroom3 knockout embryos. We preformed in silico analysis on previously identified SHROOM3 variants from patients with CHD. Results: Shroom3 null mice had Ventricular Septal Defects (0.73, p=0.0006), Double Outlet Right Ventricle (0.33, p=0.04), Left Ventricular Noncompaction, and other CHD. Shroom3 mutant mice left ventricular wall thickness was 36% thinner compared to wild type mice (99.0±8.6µm, 63.0±8.4µm, p=0.005). LacZ shows the expression of Shroom3 through important stages of cardiac development, and IHC shows actomyosin disruption. In silico analysis demonstrates CHD patients have SHROOM3 variants in highly conserved nucleic acid and protein sequences, and significant protein structural changes. Conclusion and Potential Impact: Shroom3 null mice have cardiac defects resembling a Wnt/PCP disruption phenotype. Similarly, patients with CHD have likely pathogenic variants in SHROOM3. These data support a role for SHROOM3 in CHD pathogenesis and begin to elucidate mechanisms. Identifying SHROOM3’s role in CHD is critical to understanding cardiac development as well as the diagnosis, management and treatment of CHD.
Graph analysis of looming-selective networks in the tectum, and its replication in a simple computational model

Looming stimuli evoke behavioral responses in most animals, yet the mechanisms of looming detection in vertebrates are poorly understood. Here we hypothesize that looming detection in the tectum may rely on spontaneous emergence of synfire chains: groups of neurons connected to each other in the same sequence in which they are activated during a loom. We then test some specific consequences of this hypothesis. First, we use high-speed calcium imaging to reconstruct functional connectivity of small networks within the tectum of Xenopus tadpoles. We report that reconstructed directed graphs are clustered and hierarchical, that their modularity increases in development, and that looming-selective cells tend to collect activation within these graphs. Second, we describe spontaneous emergence of looming selectivity in a computational developmental model of the tectum, governed by both synaptic and intrinsic plasticity, and driven by structured visual inputs. We show that synfire chains contribute to looming detection in the model; that structured inputs are critical for the emergence of selectivity, and that biological tectal networks follow most, but not all predictions of the model. Finally, we propose a conceptual scheme for understanding the emergence and fine-tuning of collision detection in developing aquatic animals.
Tales of abuse and negligence: current humanitarian practices and refugee children

The international community has struggled to effectively and humanely respond to the increase in forced displacement and has failed in finding effective solutions to the overwhelming immediate huma...
Adjuvant Chemotherapy With Etoposide Plus Cisplatin for Patients With Pathologic Stage II Nonseminomatous Germ Cell Tumors.

PURPOSEThe relapse rate after primary retroperitoneal lymph node dissection (RPLND) for patients with pathologic stage (PS) IIA nonseminomatous germ cell tumors (NSGCTs) is 10%-20% but increases to...
Organometallic Uranyl Complexes Featuring a Carbodicarbene Ligand

Uranyl–carbon bonds are rare due to the limited numbers of synthetic routes. The synthesis of carbodicarbene uranyl complexes is reported, along with complete spectroscopic and structural character...
Progression Maps: Conceptualizing Narrative Structure for Interaction Design Support

Interactive narratives are frequently designed for learning and training applications, such as social training. In these contexts, designers may be inexperienced in storytelling and interaction design, and it may be difficult to quickly build an effective experience, even for experienced designers. Designers often approach this problem through iterative design. To augment and reduce iteration, we argue for the utility of employing models to reason about, evaluate, and improve designs. While there has been much previous work on interactive narrative models, none of them capture aspects of the interaction design necessary for testing and evaluation. In this paper we propose a new computational model called Progression Maps, which abstracts interaction design elements of the narrative's structure and visualizes its interaction properties. We report on the model, its implementation, and two studies evaluating its use. Our results demonstrate Progression Maps' effectiveness in communicating the underlying design through an easily understandable visualization.
The Current Status of Women in Surgery: How to Affect the Future.

Importance Despite women composing half of current medical school classes, surgical specialties still struggle to attract and retain women. Even after successful recruitment into training, women surgeons continue to face gender bias and various obstacles to career advancement, including lower rates of surgical residency completion, board certification, and professional advancement. Gender inequality in medicine has drawn attention; particular consideration regarding the status of women in surgery is warranted. We review research delineating disparities and investigating the causes underlying such issues, and most importantly, we propose recommended action. Observations Recruitment of women into surgery is increasing as more women are visible in the specialty, and forthcoming measures to encourage mentorship and rectify issues related to pregnancy and burnout will likely improve this. However, obstacles to career development for women surgeons, including residency/fellowship support, mentorship/sponsorship, leadership, work-life balance, and pay equity remain. More importantly, gender discrimination continues, originating from conscious and unconscious bias, which is remedied only by recognition and deliberate correction. Several organizations have proactively recommended measures to cultivate gender equity for women surgeons, which require implementation to effect meaningful change. While the first step is recognition of the issues and underlying etiologies, further action is needed in combating such disparities and establishing a culture of equity for women in surgery. Conclusions and Relevance Opportunities for women in surgery have improved, although much work remains to make the surgical workplace supportive of women, empowering them to optimally contribute. These efforts will benefit organizations, the community, future generations of surgeons, and most importantly, profoundly and positively affect the care of patients.
Synthesis and Spectrophotometric Analysis of 1-Azafluorenone Derivatives.

A new extension for the ‘one pot’ construction of diverse 1-azafluorene derivatives featuring a Diels–Alder/retro-Diels–Alder cycloaddition is reported. Conditions were also determined for oxidation to the derived azafluorenones. The spectrophotometric analysis of five different azafluorenones were performed. Moderate fluorescence was observed with azafluorenone derivatives that bear an imbedded pyridone motif; whereas those bearing substituted pyridines do not fluoresce.
Inefficiency of anthraquinone-based avian repellents when applied to sunflower: the importance of crop vegetative and floral characteristics in field applications.

Background Blackbirds (Icteridae) cause significant damage to sunflower (Helianthus annuus L.) prompting the need for effective management tools. Anthraquinone-based repellents can reduce feeding by >80% in lab settings, but require birds to learn the negative association through repellent ingestion. We evaluated an anthraquinone-based repellent applied directly to mature sunflower plants for its ability to reduce bird damage. We used captive male red-winged blackbirds (Agelaius phoeniceus) to evaluate efficacy of two anthraquinone-based formulations in varying concentrations and applied in a manner attainable by sunflower producers. We also assessed field application methods for repellent coverage and anthraquinone residues when using ground-rigs equipped with drop-nozzles situated below the crop canopy. Results The repellents failed to reduce feeding and birds did not exhibit a preference between untreated and treated sunflowers at concentrations 2.7x the suggested application rate (i.e., 9.35 L ha-1 of repellent). In the absence of disk flowers, which obstruct repellent from reaching the achenes, the repellents failed to reduce consumption. Anthraquinone concentrations in field applications were considerably less than those in the lab experiments and did not reduce bird damage. Conclusion Efficacy is difficult to achieve in the field due to application issues where growth patterns and floral components of sunflower limit residues on achenes, thus contact with foraging birds. Although field residues could be improved by increasing anthraquinone concentrations in tank mixtures and decreasing droplet size, repellents optimized for loose achenes are inefficient in reducing avian consumption of sunflower when applied to intact plants in a manner representative of commercial agriculture. This article is protected by copyright. All rights reserved.
Improved methods for targeting epigenetic reader domains of acetylated and methylated lysine

Responsible for interpreting histone post-translational modifications, epigenetic reader proteins have emerged as novel therapeutic targets for a wide range of diseases. Chemical probes have been critical in enabling target validation studies and have led to translational advances in cancer and inflammation-related pathologies. Here, we present the most recently reported probes of reader proteins that recognize acylated and methylated lysine. We will discuss challenges associated with achieving potent antagonism of reader domains and review ongoing efforts to overcome these hurdles, focusing on targeting strategies including the use of peptidomimetic ligands, allosteric modulators, and protein degraders.
Polθ reverse transcribes RNA and promotes RNA-templated DNA repair

Genome-embedded ribonucleotides arrest replicative DNA polymerases (Pols) and cause DNA breaks. Whether mammalian DNA repair Pols efficiently use template ribonucleotides and promote RNA-templated DNA repair synthesis remains unknown. We find that human Polθ reverse transcribes RNA, similar to retroviral reverse transcriptases (RTs). Polθ exhibits a significantly higher velocity and fidelity of deoxyribonucleotide incorporation on RNA versus DNA. The 3.2-A crystal structure of Polθ on a DNA/RNA primer-template with bound deoxyribonucleotide reveals that the enzyme undergoes a major structural transformation within the thumb subdomain to accommodate A-form DNA/RNA and forms multiple hydrogen bonds with template ribose 2′-hydroxyl groups like retroviral RTs. Last, we find that Polθ promotes RNA-templated DNA repair in mammalian cells. These findings suggest that Polθ was selected to accommodate template ribonucleotides during DNA repair.
Stepwise as Opposed to Concerted Conformational Changes Optimize Signal Transmission in Allosteric Dimers

Quantifying how assemblies of molecules coordinate their motions is key to understanding the operation of biological machines and other modular nanosystems. We explore the question of how tightly coupled the motions of adjacent units should be to optimize the transmission of signals, in an environment beset by thermal fluctuations. In this paper, we consider an allosteric dimer consisting of two ligand-binding domains and study how variations of ligand binding at one site are translated to similar variations in ligand affinity at the adjacent site. We compute the dynamics using a simple energy landscape model, and using mathematical methods used to study phenomenon of stochastic resonance, quantify the fraction of signal that propagates through the allosteric system as a transmission coefficient. We find that the transmission coefficient is optimized for an intermediate coupling between domains. The intermediate coupling is a compromise—when it is too low, the motion of the domains become uncorrelated, and fidelity suffers, but when it is too high, the system must surmount multiple transition barriers to change conformation, and communication slows down. There are two consequences. First, for a wide range of energy landscape parameters, the intermediate coupling corresponds to stepwise switching of domains via high energy (1.4 kcal/mol) lowly populated (<10% occupancy) intermediates. Second, the compromise between fidelity and rate caps the transmission coefficient at 40%, so that the majority of signal is degraded, even at the most perfectly formed allosteric interface. We propose that the stepwise switching observed in many allosteric proteins does not arise from an inherent limit in the mechanical couplings within the protein, but is a consequence of optimizing signal transmission; and that in general, if signals are to be communicated between domains via conformational change, a certain looseness of coupling is preferred, to provide a useful freedom of motion.
Glucocorticoid effects on peripheral blood lymphocytes in cows infected with bovine leukemia virus

We examined the effects of glucocorticoids on peripheral blood lymphocytes (PBL) in lymphoproliferative conditions associated with bovine leukemia virus (BLV): persistent lymphocytosis (PL) and lymphosarcoma cell leukemia (BLSL). The effects of hydrocortisone 21-sodium succinate (HSS) on spontaneous incorporation (SI) and mitogen-stimulated incorporation of radiolabeled-thymidine and the effects of intramuscular administration of prednisolone acetate were studied. An expanded population of B lymphocytes in cows with PL was remarkable sensitive to glucocorticoids in vitro and in vivo. SI was markedly inhibited by concentrations of HSS as low as 10(-7) M. These results correlated well with in vivo observations, where an 80%-90% decrease in PBL occurred during the course of glucocorticoid administration. The decrease in total lymphocytes was accounted for almost entirely by a decrease in the expanded B lymphocyte population. Steroid-sensitive lymphocytes together with steroid-resistant cells were observed in cows with BLSL. The reduction in the steroid-sensitive lymphocytes was associated with rapid disease progression in cows with lymphosarcoma. Steroid-sensitive lymphocyte populations in cows with BLSL may include the same reactive B-cell population found in cows with PL. Glucocorticoids may prove to be a useful tool for study of the immune response to the oncogenic virus and lymphoma in BLV-infected cattle.
Revisiting The People and the Court

Charles Lund Black at 70 has earned his reputation: He is unquestionably among a handful whose scholarship occupies prominence in the li? brary of the law's queen subject. During the past three decades, there have been few constitutional lawyers who have written as provocatively?and none as poetically?as Charles. To attend to his writing is to see public law afresh. No one can read him, for example, on the death penalty,1 impeachment,2 segregation8 or state action4 without gaining new perspectives on our political morality. And, after a few hours with Struc? ture and Relationship in Constitutional Law,5 one is bound to under? stand better the essence of our system of government. Yet, it is my impression that Charles's book on judicial review (the queen topic of the queen subject) is sometimes cited primarily because it was written by an important scholar, with little reference to, or under? standing of, its central insights. The book's teaching, about the well estab? lished practice of subjecting governmental action to constitutional examination in the courts, often is neglected. I have just discovered that this is a terrible oversight. The People and the Courf would be an important book no matter what its pedigree?the artistic worth of The Man With the Golden Helmet does not depend on its attribution to Rembrandt. Still, it is true that no one but Charles Black could have written his book on judicial review.
Confocal Fluorescence Microscopy

This article describes basic approaches to image materials by means of optical microscopy with fluorescence markers. The fluorescence microscopy is used to image materials in which the contrast cannot be achieved by light absorption, scattering, or birefringence. The fluorescence microscopy benefits greatly from a confocal mode of observation that eliminates signal coming from outside the small region of sample that is probed by a tightly focused laser beam. By scanning the focused laser beamthrough the sample, one obtains a 3D map of density of fluorescing molecules staining the sample. This technique is called confocal laser scanning microscopy (CLSM). By using fluorescent markers of anisometric shape and a polarized laser beam, one can produce 3D images of orientationally ordered materials such as liquid crystals. In this technique, called a fluorescent confocal polarizing microscopy (FCPM), the signal depends on the angle between the transition dipole of the dye and the polarization of probing light. Recent advances in the development of fluorescent markers that can be controllably switched between the bright state and the dark state lead to revolutionary development of far-field optical microscopy with resolution well below the diffraction limit. Keywords: fluorescence; confocal laser scanning microscopy; fluorescent confocal polarizing microscopy; Nipkow disk
Chemical characterization of microparticles by laser ablation in an ion trap mass spectrometer

We are developing a new technique for the chemical characterization of microparticles based upon the use of electrodynamic traps. The electrodynamic trap has achieved widespread use in the mass spectrometry community in the form of the ion trap mass spectrometer or quadrupole ion trap. Small macroscopic particles can be confined or leviated within the electrode structure of a three-dimensional quadrupole electrodynamic trap in the same way as fundamental charges or molecular ions by using a combination of ac and dc potentials. Our concept is to use the same electrode structure to perform both microparticle levitation and ion trapping/mass analysis. The microparticle will first be trapped and spatially stabilized within the trap for characterization by optical probes, i.e., absorption, fluorescence, or Raman spectroscopy. After the particle has been optically characterized, it is further characterized using mass spectrometry. Ions are generated from the particle surface using laser ablation or desorption. The characteristics of the applied voltages are changed to trap the ions formed by the laser with the ions subsequently mass analyzed. The work described in this paper focuses on the ability to perform laser desorption experiments on microparticles contained within the ion trap. Laser desorption has previously been demonstrated in ion more » trap devices by applying the sample to a probe which is inserted so as to place the sample at the surface of the ring electrode. Our technique requires the placement of a microparticle in the center of the trap. Our initial experiments have been performed on falling microparticles rather than levitated particles to eliminate voltage switching requirements when changing from particle to ion trapping modes. « less
Peripheral T Cell Lymphoma in a Patient with Common Variable Immunodeficiency Disease: Case Report and Literature Review

This report documents the occurrence of a peripheral T cell lymphoma arising in the bone marrow and liver of a patient with common variable immunodeficiency disease. The T cell origin of this lymphoma was demonstrated by immunohistochemical phenotyping and gene rearrangement studies and was not associated with EBV infection of the lymphoma cells. The frequency and characteristics of lymphomas complicating CVID are reviewed.
The microbiota conditions CX3CR1+ intestinal mononuclear phagocytes to limit intestinal inflammation. (MUC2P.822)

Regulation of intestinal immune responses requires distinguishing normal beneficial bacteria (the microbiota) from pathogens capable of inducing disease. While it is clear that the intestine and intestinal immune system recognize and respond to the microbiota, it is unclear how this recognition influences subsequent immune responses. One intestinal antigen presenting cell population, characterized by expression of the chemokine receptor CX3CR1, has been described as tissue resident macrophages. In contrast to previous reports, we recently demonstrated that CX3CR1+ cells migrate from the intestine to the mesenteric lymph node, suggesting that they can behave as dendritic cells (DCs). By utilizing both genetically modified mice and antibiotics to manipulate the intestinal microbiota, we demonstrated that the microbiota influences intestinal immunity by modulating CX3CR1+ cells. In the presence of an intact microbiota, CX3CR1+ cells limit the induction of inflammatory immune responses. In contrast, in conditions where the microbiota has been perturbed, CX3CR1+ cells promote the induction of inflammatory immune responses. We further demonstrate that antigen presentation by CX3CR1+ cells is critical for priming T cell responses to intestinal antigens in vivo, confirming CX3CR1+ cells can act as DCs. Together, our findings indicate that CX3CR1+ cells play a central role in integrating signals from the microbiota to maintain intestinal immune homeostasis.
Enzymes, Directed Evolution

Introduction Why Directed Evolution? The Limitations of Nature's Biocatalysts Present Insurmountable Challenges to Rational Design Extending Natural Diversity by Laboratory Evolution Choosing an Evolutionary Strategy Good Problems for Directed Enzyme Evolution Methods of Directed Evolution Methods for Generating Genetic Diversity Searching for Improved Enzymes Extracting Useful Information from the Results of Evolution Examples of Directed Evolution Applications Evolution of Lipases with High Activity in Detergent Solutions Evolution of an Esterase for Deprotection of p-Nitrobenzyl Esters and Enhanced Thermostability Evolution of Herpes Simplex Virus Thymidine Kinase for Gene Therapy Evolution of Biphenyl Dioxygenases for Bioremediation of PCBs Acknowledgments Bibliography Keywords: biocatalysis; catalyst improvement; DNA shuffling; high-throughput screening; protein engineering; random mutagenesis; recombination; selection
Can computers carry content ‘inexplicitly’?

I examine whether it is possible for content relevant to a computer's behavior to be carried without an explicit internal representation. I consider three approaches. First, an example of a chess playing computer carrying ‘emergent’ content is offered from Dennett. Next I examine Cummins’ response to this example. Cummins says Dennett's computer executes a rule which is inexplicitly represented. Cummins describes a process wherein a computer interprets explicit rules in its program, implements them to form a chess-playing device, then this device executes the rules in a way that exhibits them inexplicitly. Though this approach is intriguing, I argue that the chess-playing device cannot exist as imagined. The processes of interpretation and implementation produce explicit representations of the content claimed to be inexplicit. Finally, the Chinese Room argument is examined and shown not to save the notion of inexplicit information. This means the strategy of attributing inexplicit content to a computer which is executing a rule, fails.
Passivity in Copper‐Nickel and Molybdenum‐Nickel‐Iron Alloys

Passivity in an alloy appears at a critical composition which for ferrous and copper‐nickel alloys is related to the tendency of the d band of electronic energy states to fill with electrons. According to magnetic and specific heat data, it is known that the d band of copper‐nickel is filled at 60 atom % Cu or 40 atom % Ni. Corrosion data show that transition from passivity to activity occurs at this same nickel content. Conditions of electron transfer or sharing which are described for passivity in binary combinations are essentially retained in the ternary system of molybdenum‐nickel‐iron alloys. It is shown that passivity in these ternary alloys, according to corrosion data of 28%, 35% and 60% Ni alloy series in sulfuric acid, occurs approximately at the predicted atomic ratio of Mo to Fe equal to 0.2. Molybdenum apparently can passivate either nickel or iron or both. One example is Mo 18/8, in which the 10% Ni it contains is passivated by 2% to 4% Mo. The commercial practice of adding a minimum of 2%Mo confirms the calculated value 1.8% based on the electron configuration theory. A similar calculation shows that 17.5% Mo is the minimum amount necessary for passivity in Hastelloy A, which is comparable with 20% Mo actually employed. Furthermore, the maximum percentage of iron permitted in a passive 20% Mo, balance Ni and Fe alloy, is calculated to be 35% which agrees with approximately 30% found experimentally. The successful correlation of electron configurations of atoms and theories of the metallic state with corrosion behavior suggests a new approach to the general problem of passivity in metals and in alloys.
A two-dose epidural morphine regimen for cesarean section patients: therapeutic efficacy.

A single dose of epidural morphine (EM) usually produces 24 h of post-cesarean section (CS) analgesia and patients require supplemental analgesics beyond this period. This study assesses if a second dose of EM administered 24 h after the first one offers superior therapeutic efficacy compared to conventional analgesics. Patients (n = 100) were randomized to receive one or two doses of epidural morphine. In all patients, EM 5 mg was administered after delivery. After 24 h patients received epidurally either normal saline (n = 50, Group 1) or morphine 5 mg (n = 50, Group 2). An independent observer used a visual analogue scale to assess nausea, itching, and analgesia 24 h after each injection. Results were expressed as mean +/- 1 s.e. mean and analyzed using nonparametric methods. The second dose of EM produced a significantly lower incidence and severity of nausea and itching than did the first dose (P < 0.01) in Group 2 with no difference in analgesia. The second day postoperative pain score in Group 1 was significantly greater than the first day score in the same group, and significantly greater than the severity score in Group 2. Only 36% of patients receiving two doses of EM required supplemental analgesics beyond 48 h compared to 76% of those receiving one dose (P < 0.01). No serious complications were noted. In summary, the use of a second dose of EM for post-CS analgesia produces better analgesia and reduces the need for oral analgesics. The second dose produced fewer side-effects, probably due to acute tolerance to morphine.
L-selectin defines a bone marrow analog to the thymic early T-lineage progenitor.

The recent description of an early T-lineage progenitor (ETP) population in adult mouse thymus implies the presence of a bone marrow predecessor that has not yet been identified. Here we describe a LinNeg Sca-1Pos c-kitHi Thy-1.1Neg L-selectinPos adult mouse bone marrow population that resembles the thymic ETP in both antigen expression phenotype and posttransplantation lineage potential. These cells produce wavelike kinetics of thymic seeding and reconstitute the irradiated thymus with kinetics comparable to a thymocyte graft after intravenous transplantation. Transient B-lineage reconstitution is also observed, but little myeloid potential can be detected in transplant experiments. A second subset of progenitors is L-selectinNeg and is highly enriched for rapid and persistent T- and B-lineage potential, as well as some myeloid potential. L-selectin (CD62L) is therefore an effective marker for separating lymphoid progenitors from myeloid progenitors and hematopoietic stem cells in mouse bone marrow. (Blood. 2004;103: 2990-2996)
Agroforestry development: An environmental economic perspective

Agroforestry systems (AFS) provide a mix of market goods and nonmarket goods and services. We postulate that if nonmarket goods and services can be internalized to the benefit of landowners, the adoption of AFS will increase. Using the theory of externality as a conceptual framework, this paper provides an environmental economic logic for developing incentive policies to internalize environmental services especially in the industrialized countries. Specifically, the paper addresses the following questions with focus on North America in general and southern United States in particular: What is the effect of environmental costs and benefits on the adoption of silvopasture? Do households care for carbon sequestration, water quality improvement, and biodiversity associated with silvo-pasture? Will they be willing to pay for them? If so, how much? Will ranchers adopt more silvopasture if incentives are provided? Which incentive policy, a price premium or a direct payment, is more effective? It has been found that the profitability of silvopasture would increase, relative to conventional ranching, if environmental services are included. Estimates of public willingness to pay for environmental services associated with silvopasture and estimates of ranchers’ willingness to accept for the adoption of silvopasture will provide a scientific basis for policy development.
Narrating the dialogical self: Toward an expanded toolbox for the counselling psychologist

A conception of the self as arising in narrative and sustained and transformed in dialogue carries novel implications for understanding the nature of client difficulties and resources and how change might be fostered in the counselling context. In this paper I comment on these implications, and extend their practical import by reviewing several specific tools for both reflecting upon and enacting narrative and dialogical processes that maintain and transform problem patterns. In particular, I present and illustrate a “Chapters of our Lives” technique whose aim is to articulate and potentially deconstruct client constructions of their experience across time, as well as a form of “externalized problem interviewing” that helps clients perform, and ultimately resist, the influence of the symptom or difficulty on them. These and numerous other methods more briefly described can help augment the toolbox of techniques available to counselling psychologists approaching their work from a broadly postmodern perspec...
State automorphisms in axiomatic quantum mechanics

A new metric which we call the ‘intrinsic metric’ is introduced on the statesℐ of the generalized logic of quantum mechanics. It is shown that every automorphism onℐ is an isometry. A norm can be defined on the linear spanE ofℐ which reduces to the intrinsic metric onℐ. IfX is the completion ofE then every automorphism, onℐ has a unique extension to a linear isometry onX. A comparison is made between these results and those of Kroniff.
Struggles of new college graduates in their first software development job

How do new college graduates experience their first software development jobs? In what ways are they prepared by their educational experiences, and in what ways do they struggle to be productive in their new positions? We report on a "fly-on-the-wall" observational study of eight recent college graduates in their first six months of a software development position at Microsoft Corporation. After a total of 85 hours of on-the-job observation, we report on the common abilities evidenced by new software developers including how to program, how to write design specifications, and evidence of persistence strategies for problem-solving. We also classify some of the common ways new software developers were observed getting stuck: communication, collaboration, technical, cognition, and orientation. We report on some common misconceptions of new developers which often frustrate them and hinder them in their jobs, and conclude with recommendations to align Computer Science curricula with the observed needs of new professional developers.
Independent metering of pneumatic actuator for passive human power amplification

In this paper, a method for passive human force amplification with independent metering of valves in a pneumatic actuator is reported. Unlike single valve metering, two independent valves are used to regulate the operating pressure of the actuator. The advantage of independent valves is that they can be controlled such that the actuator operates at minimum possible pressure, while providing a desired force profile. This results in reduction of the energy loss associated with discharge of high pressure air to the atmosphere thereby improving efficiency of operation. A pressure minimization scheme on the discharging side of the actuator is proposed to achieve minimum operating pressure. Passive human power amplification is achieved by commanding suitable inputs to the valve on the high pressure side. An experimental comparison with single valve metering shows that independent metering improves the operating time by nearly 100%, thus improving the efficiency of operation.
The quadratic variation of Brownian motion on a time scale

Abstract The quadratic variation of a Brownian motion indexed by a nonempty closed subset of the reals, i.e. a time scale, is investigated and examples are given for various time scales to illustrate the result.
Diminished Immune Response in Sun-Damaged Skin

In previously sensitized volunteers, higher concentrations of 2,4-dinitrochlorobenzene were necessary to elicit positive patch test reactions on the sun-damaged skin of the neck than on the protected skin of the upper part of the back. This difference was not found in subjects without evidence of sun damage, and there was no difference between sun-damaged and nondamaged skin in response to a primary irritant. Responses to intradermally injected common antigens were also less intense in sun-damaged skin that in nonexposed skin. These findings suggest the existence of a local defect in cell-mediated immunity in skin altered by long-term sun exposure.
Ethical Issues in the Use of Control Groups.

Is it ethical to select clients at random for a beneficial social service, then deny the benefits to a control group for the sake of science?
Concentration effects in mesoscopic simulation of coarsening

The self-organization of particles in a two-phase system in the coexistence region through a diffusive mechanism is known as Ostwald ripening. A mesoscopic model derived from the spin exchange Ising model is used here in a computational study of Ostwald ripening. The typical cluster size is observed to grow like Lifshitz-Slyozov growth law over an early range of times with faster growth at later times. The effect of changing the concentration of particles on the morphological evolution of the system is also discussed.
Detection and Quantitation of Succinimide in Intact Protein via Hydrazine Trapping and Chemical Derivatization

The formation of aspartyl succinimide is a common post-translational modification of protein pharmaceuticals under acidic conditions. We present a method to detect and quantitate succinimide in intact protein via hydrazine trapping and chemical derivatization. Succinimide, which is labile under typical analytical conditions, is first trapped with hydrazine to form stable hydrazide and can be directly analyzed by mass spectrometry. The resulting aspartyl hydrazide can be selectively derivatized by various tags, such as fluorescent rhodamine sulfonyl chloride that absorbs strongly in the visible region (570 nm). Our tagging strategy allows the labeled protein to be analyzed by orthogonal methods, including HPLC-UV-Vis, liquid chromatography mass spectrometry (LC-MS), and SDS-PAGE coupled with fluorescence imaging. A unique advantage of our method is that variants containing succinimide, after derivatization, can be readily resolved via either affinity enrichment or chromatographic separation. This allows further investigation of individual factors in a complex protein mixture that affect succinimide formation. Some additional advantages are imparted by fluorescence labeling including the facile detection of the intact protein without proteolytic digestion to peptides; and high sensitivity, for example, without optimization, 0.41% succinimide was readily detected. As such, our method should be useful for rapid screening, optimization of formulation conditions, and related processes relevant to protein pharmaceuticals.
A rotor-stator cross-link in the F1-ATPase blocks the rate-limiting step of rotational catalysis

The F0F1-ATP synthase couples the functions of H+ transport and ATP synthesis/hydrolysis through the efficient transmission of energy mediated by rotation of the centrally located γ, ϵ, and c subunits. To understand the γ subunit role in the catalytic mechanism, we previously determined the partial rate constants and devised a minimal kinetic model for the rotational hydrolytic mode of the F1-ATPase enzyme that uniquely fits the pre-steady state and steady state data (Baylis Scanlon, J. A., Al-Shawi, M. K., Le, N. P., and Nakamoto, R. K. (2007) Biochemistry 46, 8785-8797). Here we directly test the model using two single cysteine mutants, βD380C and βE381C, which can be used to reversibly inhibit rotation upon formation of a cross-link with the conserved γCys-87. In the pre-steady state, the γ-β cross-linked enzyme at high Mg·ATP conditions retained the burst of hydrolysis but was not able to release Pi. These data show that the rate-limiting rotation step, kγ, occurs after hydrolysis and before Pi release. This analysis provides additional insights into how the enzyme achieves efficient coupling and implicates the βGlu-381 residue for proper formation of the rate-limiting transition state involving γ subunit rotation.
Predictors of Entry into Age-Discordant Relationships Among Adolescent Girls

Teenage girls in age-discordant relationships remain of concern for healthy development and well-being. We examine whether factors from several sociological frameworks—self-esteem, deviance, social ecology, family cohesion, and religious involvement—predict entry into such relationships. With longitudinal data on 1,537 adolescent girls, we use structural equation modeling to assess risk and protective factors by age group. Results indicate that few social factors predict entry to such relationships; only religious involvement for the youngest adolescents and self-esteem for middle adolescents predict entry. While adolescent girls who date older males are largely like their peers, any impact of social factors may vary by the developmental stage that adolescent girls occupy.
Technetium-99m 2-Methoxyisobutyl isonitrile-scintigraphy: Preoperative and Intraoperative Guidance for Primary Hyperparathyroidism

As refinement of technetium-99m 2-methoxyisobutyl isonitrile-scintigraphy (MIBI)-scintigraphy of parathyroid glands has continued since its initial use in 1989, the sensitivity, specificity, and overall accuracy of the technique have improved greatly, approaching 100% for larger, solitary adenomas. Preoperative use of sestamibi scintigraphy has become commonplace and allows surgeons the option of a minimally invasive, or focused approach for their patients with primary hyperparathyroidism. Intraoperative use of the gamma probe based on sestamibi localization has not caught on due to lesser accuracy, cumbersome gamma probes, small doses of radiation exposure for patients and staff, and the greater accuracy and current confidence in intraoperative parathormone (PTH) monitoring. However, with the potential for smaller and more accurate gamma probes that truly assist in localizing abnormal parathyroid glands, the potential for cost reduction by shortening operative times, avoiding expensive PTH assays, and eliminating the need for pathologic analysis, gamma scintigraphy may yet become a viable option for many parathyroid surgeons.
Study of crystallization kinetics by temperature-modulated DSC☆

Abstract A method of temperature-modulated differential scanning calorimetry (TMDSC), proposed by Toda et al., is used to study the crystallization kinetics of a polyester-imid, namely poly(4,4′-phthaloimidobenzoyldodecamethyleneoxycarbonyl). The polymer shows one irreversible melting/crystallization transition and one smaller, partially reversible transition. The experimental results prove that with this method one can obtain an important parameter that characterizes polymer crystallization via the temperature-dependence of the crystal-growth rate. The TMDSC data consist of the total heat flow, the magnitude of the apparent heat capacity, and the change of the phase lag of the heat flow in the transition region. No specific assumptions are made about the crystallization kinetics.
Dermatochalasis and blepharochalasis of the upper lids

Dermatochalasis and blepharochalasis of the upper lids, in addition to producing a cosmetic defect, causes asthenopic symptoms. A blepharoplasty for dermatochalasis removes skin only. Blepharochalasis removes protruding fat, tightens the orbital septum, and, in addition, when indicated removes excess skin. The surgical techniques for these procedures are presented.
INFECTIOUS CATARRH OF MICE III. THE ETIOLOGICAL SIGNIFICANCE OF THE COCCOBACILLIFORM BODIES

Evidence is presented that the etiology of infectious murine catarrh is specifically referable to the coccobacilliform bodies. The disease was regularly produced in normal mice by the nasal instillation of primary tissue cultures. In the presence of the X bacillus, transfers of primary cultures were usually uninfective. Pure cultures, however, retained their pathogenicity through as many as 12 transfers. The onset and progress of the experimental disease were somewhat retarded in comparison with the natural disease, but in general there was a close parallel. Mice injected with cultures did, however, show a significant decrease in the incidence of rhinitis. Transmission by direct contact was demonstrated in the presence of a rhinitis but not in its absence.
Shifting sands: Explaining and predicting phase shifts by dissident organizations

Why does a dissident group go through phases of violence and nonviolence? Many studies of states and dissidents examine related issues by focusing on structural or rarely changing factors. In contr...
Doppler Myocardial Imaging for Early Detection of Right Ventricular Dysfunction in Patients With Pulmonary Hypertension

Background In pulmonary hypertension (PHT), right ventricular (RV) function affects treatment strategy and prognosis. Doppler myocardial imaging (DMI) has the potential to detect early RV dysfunction. Methods Regional RV function was prospectively assessed in 110 patients without primary structural heart disease, including patients with known PHT (group I; n=40; mean age, 59 ± 16 years) and tricuspid regurgitation (TR) velocity ≥ 3 m/s; group II (n = 30; mean age, 57 ± 13 years), with TR velocity > 2.5 to Results Basal RV peak systolic strain and strain rate (SR) were correlated with TR velocity ( r = 0.59 and r = 0.49, respectively; P r = 0.53 and r = 0.45, respectively; P P = .016; −1.6 ± 0.4 vs −1.9 ± 0.5 s −1 , P = .004; and −1.2 ± 0.2 vs −1.4 ± 0.1 s −1 , P Conclusions RV and septal systolic strain and SR may allow the recognition of early RV dysfunction in patients with PHT, even when conventional RV systolic parameters are normal.
The bigger the crisis, the bigger the opportunity!

Abstract Every time I pick up the newspaper, a scientific or nursing journal, or more recently, an issue of Time, I find data, complete with startling facts and figures, that pierce my very soul, about the tragedies occurring in our nation's hospitals caused by the restructuring movement attempting to make health care a “bottom line” business. And 1 know all too well, as do most of you, how undetermined and tentative we are about the future for nurses.
Education Quality in the Middle East

Some of the most dramatic growth in the provision of primary and secondary education over the last decade has occurred across countries of the Middle East and North Africa (MENA). Yet student achievement across MENA is lagging compared to many other parts of the world. Low quality of education is a primary concern and one of the greatest challenges facing education and government leaders across the region. This paper summarises recent evidence regarding student learning in the MENA region and draws on Galal’s model of policy formulation in considering ways that governments across the Middle East might address this problem.
State-Specific Legal Research Instruction: Curricular Stepchild or Core Competency?

The authors argue that proficiency in state-specific legal research is a competency all law students should attain in law school, for the primary reason that many (if not most) students begin practice in the state where they attend law school, a reality of even those who attend so-called national law schools. Ten state-specific legal research courses currently offered are discussed by the authors, who also present a model syllabus for a one, two, and three unit state-specific legal research course.
A Risk‐Reward Framework for the Competitive Analysis of Financial Games

Competitive analysis is concerned with minimizing a relative measure of performance. When applied to financial trading strategies, competitive analysis leads to the development of strategies with minimum relative performance risk. This approach is too inflexible. Many investors are interested in managing their risk: they may be willing to increase their risk for some form of reward. They may also have some forecast of the future. In this paper we extend competitive analysis to provide a framework in which investors can develop optimal trading strategies based on their risk tolerance and forecast. We first define notions of risk and reward that are natural extensions of classical competitive analysis and then illustrate our ideas using the ski-rental problem. Finally, we analyze a financial game using the risk—reward framework, and, in particular, derive an optimal risk-tolerant algorithm.