cssi/SciSciGPT-SciSciNet huggingface dataset:
Production of Fully Active Recombinant Murine Granzyme B in Yeast

Granzyme B (GzmB) is a neutral serine protease found in cytotoxic lymphocytes; this enzyme is critically involved in delivering the rapid apoptotic signal to susceptible target cells. GzmB has been difficult to study and has not yet been produced in non-mammalian systems because of the complex processing events that are thought to be required for its activation. In this report, we have successfully produced fully active, soluble recombinant GzmB (rGzmB) in a yeast-based system by fusing GzmB cDNA in frame with yeast alpha-factor cDNA, using the yeast KEX2 signal peptidase to release the processed enzyme into the supernatant of yeast cultures. We expressed the proenzyme form of GzmB as well and determined that pro-GzmB is efficiently converted to its active form by the cysteine proteinase dipeptidyl peptidase I. The fully processed enzyme was able to hydrolyze the synthetic substrate N-t-butyloxycarbonyl-L-alanyl-L-alanyl-L-aspartyl (Boc-Ala-Ala-Asp) thiobenzyl ester with a kcat of 17 s-1 and catalytic efficiency kcat/Km of 181,237 M-1 S-1; the recombinant enzyme is therefore at least twice as active as purified native GzmB. In addition, the recombinant enzyme hydrolyzes Boc-Ala-Ala-Met thiobenzyl ester with a kcat of 3.2 S-1 and a catalytic efficiency kcat/Km of 65,306 M-1 S-1. Purified rGzmB can also cleave the putative substrate caspase-3 into its signature p20/p10 forms. Unlike caspases, rGzmB is not sensitive to inhibition by several peptide-based inhibitors, including Ac-DEVD-CHO, Ac-YVAD-CMK, and ZIETD-FMK, as well as Zn2+ (a known inhibitor of caspase-3). Structural studies of rGzmB may allow us to better understand the substrate specificity of this enzyme and to design better inhibitors.
The management of duodenal and other small intestinal trama

One hundred sixty-three patients were treated for blunt and penetrating trauma of the duodenum and small bowel over a 41/2-year period at a major trauma center. Blunt injuries, mostly a result of vehicular trauma, comprised 17% of the cases, while stabbing and firearm injuries made up the remainder. Laboratory data, including white blood cell count, amylase, and abdominal x-rays, were unreliable in predicting the presence of intestinal injury. Although only obtained in a few patients following blunt injury, computerized tomography (CT scan) of the abdomen was sensitive to intraperitoneal findings suggestive of or diagnostic for gastrointestinal injury. Speedy operative management is of the utmost importance; 63% of these patients were operated on in less than 2 hours from the initiation of medical treatment. The majority of intestinal damage can be repaired by simple closure or resection. Because of anatomic and physiologic considerations, complex operative procedures are required for the correction of some duodenal lesions. Our treatment of these injuries included frequent utilization of pyloric exclusion, as well as occasional diverticulization of the duodenum and pancreaticoduodenectomy. Delay in treatment and the magnitude and number of associated injuries contributed to increased morbidity and mortality, which was much higher in blunt trauma (21% versus 4% for penetrating injuries), especially when the duodenum was involved (36% mortality). Complications were also more common in the patients following blunt trauma and with multiple injuries. Infectious complications were the most frequent, with postoperative ileus or obstruction, hemorrhage, and iatrogenic complications occurring less often. In the majority of small bowel injuries, the management is straightforward and consists of operative repair as soon as possible. A high index of suspicion and reliance on diagnostic aids, such as CT scan, will speed the diagnosis of occult blunt intestinal injuries. Sound surgical judgment and facility with a variety of repairs is needed in the treatment of complex duodenal injuries.
Fractionalized non-self-dual solutions in the CP N-1 model

We study non-self-dual classical solutions in the ${\mathbb{C}\mathbb{P}}^{N\ensuremath{-}1}$ model with ${\mathbb{Z}}_{N}$ twisted boundary conditions on the spatially compactified cylinder. These solutions have finite, and fractional, classical action and topological charge, and are ``unstable'' in the sense that the corresponding fluctuation operator has negative modes. We propose a physical interpretation of these solutions as saddle point configurations whose contributions to a resurgent semi-classical analysis of the quantum path integral are imaginary nonperturbative terms that must be cancelled by infrared renormalon terms generated in the perturbative sector.
Skeletal and cardiovascular lesions in turkeys induced by feeding beta-aminopropionitrile.

Abstract Beta-aminopropionitrile toxicosis in turkeys induced skeletal and cardiovascular lesions. Enlarged hocks with widening of the epiphyseal plate and articular cartilage, green tinting of the skin over swollen joints, and synovitis were the skeletal defects that were found. Joint lesions apparently resulted from impediment of endochondral mineralization and maturation of chondrocytes in the epiphyseal plate and articular cartilage. Cardiovascular alterations resulting from BAPN feeding included ground substance increase, swelling and disorganization of collagenous fibers, and elastolysis. These changes cause polypoid intimal thickenings and the induction of dissecting aneurysms. Intimal arteriosclerotic plaques were found in the posterior aorta of “normal” turkey poults. There is a possibility that such lesions are a prerequisite for the development of dissecting aneurysms.
New calculation of the numerical value of the lamb shift

Abstract The calculation of the second-order perturbation in hydrogen which gives the low-energy part of the Lamb Shift is attacked from a new approach, described in the preceding papers and here extended. A formula is gotten for ln(k0) involving a double integral. The final numerical evaluation using an electronic computer to sum the series expansion of this formula yields what we believe to be the most accurate value of ln(k0) yet given. Small discrepancies with the earlier results of Harriman are outside the realm of current physical significance, but do indicate that the reliability of the earlier results was badly overestimated. Approximate formulas for the radiative-perturbed wave functions are given; these may be quite useful for further calculations.
Pressure dependence of the magnetisation of YFe2 and ZrFe2: computation and experiment

Values of delta ln sigma / delta P, where sigma is the magnetisation per unit mass, for YFe2 (ZrFe2) of -8.4+or-0.4 (-6.3+or-0.3)*10-4 kbar-1 were obtained from forced magnetostriction measurements on polycrystalline samples at 4.2K in fields of up to 12 T. These values are shown to be in reasonable agreement with ab initio computer calculations of delta ln sigma / delta P but contradict earlier experimental work. The agreement between experiment and theory for delta ln sigma / delta P provides further evidence that YFe2 and ZrFe2 are ferrimagnetic.
A comprehensive error compensation system for correcting geometric, thermal, and cutting force-induced errors

A comprehensive error compensation system has been developed to correct geometric, thermal, and cutting force-induced errors on a turning centre. The basic approach to error compensation is proposed in this paper. The implementation of error compensation control and of hardware configuration of the system are also presented. A total of 11 geometric and thermal error components and 10 cutting force-induced error components can be compensated for using this system. Performance evaluations have been carried out using actual cutting tests. Experimental results show that the diameter accuracy of the part has been improved more than 5 times and taper accuracy of the part has been improved about 5 times.
Monoclonal antibody therapies targeting immune checkpoints induce fatal anaphylactic reactions in a murine model of breast cancer

Co-inhibitory molecules such as PD1, PD-L1 and CTLA-4 are being increasingly used as targets of therapeutic intervention against cancer. The use of monoclonal antibodies targeting these immune checkpoints has been shown to promote anti-tumor immune responses clinically. While these promising results have led to a critical paradigm shift in treatments for cancer, these approaches are also plagued with limitations owing to cancer immune evasion mechanisms and adverse toxicities associated with continuous treatment. It has been difficult to reproduce and develop interventions to these findings preclinically for many reasons including species/age-related differences in expression of these markers, poor tumor modeling, and reagent xenogenicity. In this study, we investigated adverse effects in mice receiving repeated anti-PD1 (clone J43) or PD-L1 (clone 10F.9G2) monoclonal antibody (mAb) administration in the 4T1 mouse model of mammary carcinoma. Mice bearing day 14 syngeneic mammary carcinomas were treated with mAbs to PD1 or PD-L1 which are of rat or hamster origin respectively. Control mice received rat IgG or hamster IgG mAb. Repeat administration of 250 mg i.p. of anti-PD1 or 200 mg i.p. of anti-PD-L1 into tumor bearing mice led to mortality in 50-100% of treated mice within 10 days of the initiation of treatment whereas mice receiving the control mAbs exhibited complete survival at equivalent doses. These toxicities were observed within 1-5 hours of administration of the final dose. Consistent with anaphylaxis, symptoms including piloerection, periorbital puffiness and dyspnea were observed prior to mortality. Furthermore, spleens of mice treated with anti-PD1 were observed to be greater in size relative to untreated mice indicating increased myelopoiesis. Previously, 4T1 has been associated with high expression of granulocyte-colony stimulating factor (G-CSF) systemically resulting in increased extramedullary hematopoiesis and the accumulation of myeloid derived suppressor cells (MDSCs). Both G-CSF and MDSCs have been shown to play an exacerbating role in anaphylactic reactions. Our observations here suggest that the foreign nature of anti-PD1 and anti-PD-L1 along with their important role in checkpoint blockade combined with tumor-induced immune modulation may promote an anaphylaxis-like response in tumor-bearing mice. This study highlights the importance of species-specific mAbs for preclinical models as well as the interesting roles of both checkpoint blockade and tumor-dependent immunomodulation contributing to this particular class of cancer immunotherapy.
Gesture and language dialectic

Abstract A classic psycholinguistic problem is parole, in its modern formulation, ‘performance’. This paper looks at aspects of parole or performance from a new direction, arguing that it is organized as a dialectic of unlike cognitive modes, a dialectic of gesture imagery and language. This dialectic is the key to the evocation, organization, and ultimate execution of meaningful actions shaped to take linguistic form in discourse — imagery, as embodied in the gestures that accompany speech, and the categorical-sequential thinking of speech itself. Both modes are essential components of psycholinguistic performance. A dialectic moreover naturally incorporates the context of speaking in an integral way and we shall develop a theoretical description of context as part of the analysis of performance. Such a dialectic model is self-motivating, self-directed and does not need a guiding hand (hidden or otherwise) of an executive.
Evidence-based practice part 1: Pain definitions, pathophysiologic mechanisms, and theories

Evidence-based practice consists of using research evidence to validate patient care. A body of evidence exists on pain mechanisms and pain management; however, patients continue to experience unrelieved pain. This 3-part series on pain will explore evidence in pain theories, pathophysiological mechanisms, instruments to measure pain, and how to manage pain in PACU patients.
Finite element implementation of virtual internal bond model for simulating crack behavior

The virtual internal bond (VIB) model has been recently proposed to describe material deformation and failure under both static and dynamic loading. The model is based on the incorporation of a cohesive type law in a hyperelastic framework, and is capable of fracture simulation as a part of the constitutive formulation. However, with an implicit integration scheme, difficulties are often encountered in the finite element implementation of the VIB model due to possible negative eigenvalues of the stiffness matrix. This paper describes the implementation of an explicit integration scheme of the VIB model. Issues pertaining to the implementation, such as mesh size and shape dependence, loading rate dependence, crack initiation and growth characteristics, and solution time are examined. Both quasi-static and dynamic loading cases have been studied. The experimental validation of the VIB model has been done by calibrating the model parameters using the experimental data of Andrews and Kim [Mech. Mater. 29 (1988) 161]. The simulations using the VIB model are shown to agree well with the experimental observations.
The effects of maternal modeling and negative familial communication on women's eating attitudes and body image

This research examined negative familial communication as a moderator of the relationship between maternal modeling and daughters' eating attitudes and body image after controlling for Body Mass Index (BMI) and family environment. Participants were 103 college-aged women and their mothers. Following informed consent, mothers and daughters completed the demographic questionnaire, the Negative Familial Communication items, the Body Shape Questionnaire (BSQ; Cooper, Taylor, Cooper, & Fairburn, 1987 ), and the Eating Attitudes Test (EAT; Garner & Garfinkel, 1979 ). Daughters also completed the Family Environment Scale (FES; Moos & Moos, 1986 ). Three components comprised the maternal modeling variable: past and present dieting behaviors, body image dissatisfaction, and maladaptive eating attitudes and behaviors. Results indicated that negative familial communication moderated the relationship between maternal modeling and daughters' eating attitudes and body image; the influence of maternal modeling was significant at high levels of negative familial communication but not at low levels of negative familial communication. These results may clarify the equivocal findings with respect to modeling in past research and suggest that negative familial communication should be assessed when examining the role of modeling in the development of eating- and weight-related disturbances.
Transient lesion in the splenium of the corpus callosum in status migrainosus

A 10-year-old Caucasian boy presented to the pediatric emergency room with continuous severe bitemporal throbbing headache, photophobia, phonophobia and vomiting for 7 days. He also endorsed some intermittent right leg and foot numbness. He was diagnosed with migraine without aura 6 months back fulfilling the required criteria of the International Classification of Headache Disorders, 3rd edition. His intermittent headaches prior to this presentation were easily controlled with nonsteroidal antiinflammatory drugs. There was no history of fever, concussion or any other sick symptoms. MRI of brain revealed focal area of restricted diffusion in the splenium of the corpus callosum with corresponding T2 and flair hyperintensity (Fig. 1a, b). During further evaluation, repeat brain MRI next day showed resolution of the restricted diffusion but T2 and flair hyperintensity persisted. Laboratory tests including hemogram and basic metabolic panel including renal function and serum electrolytes were within normal limits. MR angiography of the brain, extensive stroke workup and EEG were unremarkable. The patient was treated with IV ketorolac and valproic acid with prompt resolution of headache. He was started on low dose of amitriptyline. Follow-up MRI at 3 months showed interval resolution of the long TR signal abnormality also. Followup over 3 years showed only one to two episodes of easily controllable migrainous headache each month. Transient splenial lesions (TSL) are oval homogeneous, non-hemorrhagic and non-enhancing lesions over the central part of the splenium. This entity was first described in 1996 in association with epilepsy [1]. Afterward, reversible splenial lesion has been described with other varied etiologies, including sudden withdrawal of antiepileptic drugs,
Double-blind placebo controlled randomized trial of indomethacin on urodynamic values measured by radionuclide imaging.

The effect of the prostaglandin synthetase inhibitor, indomethacin on urodynamic values measured by radionuclide imaging was studied in 17 men in a double-blind placebo controlled randomized trial. Measurements were made of voiding time, time for 50% emptying, average flow rate, ejection fraction, post-void residual urine volume, voided volume, and total bladder volume. Statistical analyses indicated no placebo—indomethacin differences between the two groups. Although prostaglandins are thought to contribute to the act of micturition by maintenance of bladder tone and contractility, our studies indicate that a standard dose of the prostaglandin inhibitor, indomethacin, did not affect the voiding component of bladder function. Patients need not discontinue prostaglandin inhibitors and other nonsteroidal anti-inflammatory drugs with such effects prior to urodynamic testing.
Gas-Phase Synthesis of Boronylallene (H2CCCH(BO)) under Single Collision Conditions: A Crossed Molecular Beams and Computational Study.

The gas phase reaction between the boron monoxide radical (11BO; X2Σ+) and allene (H2CCCH2; X1A1) was investigated experimentally under single collision conditions using the crossed molecular beam technique and theoretically exploiting ab initio electronic structure and statistical (RRKM) calculations. The reaction was found to follow indirect (complex forming) scattering dynamics and proceeded via the formation of a van der Waals complex (11BOC3H4). This complex isomerized via addition of the boron monoxide radical (11BO; X2Σ+) with the radical center located at the boron atom to the terminal carbon atom of the allene molecule forming a H2CCCH211BO intermediate on the doublet surface. The chemically activated H2CCCH211BO intermediate underwent unimolecular decomposition via atomic hydrogen elimination from the terminal carbon atom holding the boronyl group through a tight exit transition state to synthesize the boronylallene product (H2CCCH11BO) in a slightly exoergic reaction (55 ± 11 kJ mol–1). Statist...
Symptomatic neonatal tetralogy of Fallot: repair or shunt?

Background The management of neonates with symptomatic tetralogy of Fallot (TOF) requiring surgical intervention in the first month of life remains controversial. We reviewed our experience with neonates 30 days or greater with TOF from 2002 to 2008 requiring surgical intervention. Methods Thirty-seven consecutive symptomatic nonrandomized neonates with TOF or its variants (including TOF with complete atrioventricular septal defect or absent pulmonary valve but excluding pulmonary atresia) had either a shunt (n = 17) or primary repair (n = 20). The shunted patients more commonly required emergency operation (24% vs 0%; p = 0.036); otherwise, the two groups were similar. Results One infant with preoperative bowel ischemia died one day postoperatively after emergency shunting. There were two late deaths 11 and 12 months postoperatively, both in primary repair patients. The 16 surviving shunted patients had TOF repair 216 ± 99 days after the original shunt. The shunted patients had shorter intensive care unit and hospital stays for the first operation, which became equivalent when the second hospitalization (repair) values were added. The primary repair patients more frequently had a transannular patch and a tendency to more frequent delayed sternal closure. Four primary repair (20%) and two shunted (12.5%) patients required subsequent cardiac operations after complete repair ( p = not significant). Conclusions Shunting or primary repair of neonates with symptomatic TOF provides equivalent mortality and results. Shunted patients had fewer transannular patch repairs despite having more emergent initial operations. Compared with the primary repair group, shunted patients had decreased intensive care unit and hospital stays for the first hospitalization, which were neutralized when the second operation (repair) values were added.
AC133-2, a novel isoform of human AC133 stem cell antigen.

Human AC133 antigen, also called CD133, was recently identified as a hematopoietic stem cell marker. However, the molecular structure and function of this protein has remained unclear. Here we cloned and identified a novel isoform of AC133, which we named AC133-2. In comparison to the reported AC133 cDNA, which is referred to herein as AC133-1, a small exon of 27 nucleotides is deleted in AC133-2 by alternative mRNA splicing. Similar to the previously characterized AC133 antigen, recombinant AC133-2 expressed in 293 cells was glycosylated and transported to plasma membrane. AC133-2 mRNA was found predominant in a variety of human fetal tissue, adult tissues, and several carcinomas. In contrast, AC133-1 mRNA was more prominent in fetal brain and adult skeletal muscle but was not detected in fetal liver and kidney, adult pancreas, kidney, and placenta, suggesting different roles for the two isoforms in fetal development and mature organ homeostasis. Here, we demonstrate that AC133-2 is the isoform expressed on hematopoietic stem cells derived from fetal liver, bone marrow, and peripheral blood. The results indicate that AC133-2, not AC133-1, has been the cell surface antigen recognized by anti-AC133 monoclonal antibodies that are used for isolation of hematopoietic stem cells. To further investigate its expression in other stem cell populations, we found that AC133-2 co-expressed with β1 integrin in the basal layer of human neonatal epidermis. AC133-2+/β1 integrin+ cells proliferated and differentiated in culture, which coincided with a loss of AC133-2 and gain in a terminal differentiation marker involucrin. Taken together, these results suggest that AC133-2 is expressed in multiple stem cell niches and may provide a means to isolate specific stem cell subpopulations from human tissues.
The Efficacy of Oral Appliances in the Treatment of Persistent Sleep Apnea After Uvulopalatopharyngoplasty

Twenty-four patients who failed uvulopalatopharyngoplasty (UPPP) for obstructive sleep apnea (OSA) had an adjustable oral (Herbst) appliance made to treat the persistent apnea. Six patients discontinued the device prior to sleep evaluation. Eighteen patients had polysomnographic evaluations at baseline, post-UPPP, and with the Herbst appliance in place. The apnea-hypopnea index baseline (AHI) and arterial oxygen saturation (SaO 2 ) nadir were 42.3±6.1 and 83.6±1.8%, respectively. There was no significant change in either parameter with surgery. With the oral appliance, the AHI fell to 15.3±4.4 (p≤0.01) and the SaO 2 nadir increased to 87.9±1.2% (p≤0.05). Ten of the patients had control of the OSA with the Herbst appliance with a fall in the AHI to 50% fall in AHI compared with baseline and post-UPPP values. All but one of the responders and partial responders had complete resolution of subjective symptoms of daytime sleepiness with the appliance. An adjustable oral appliance appears to be an effective mode of therapy to control OSA after an unsuccessful UPPP.
A SHIFT IN EMPHASIS IN A PSYCHIATRIC SERVICE

Abstract The traditional emphasis in psychiatry in Britain is on symptoms. In one of three clinical teams serving mixed urban and rural areas this emphasis was shifted to personal psychiatry by encouraging patients to talk about their life situation (especially the family) and by encouraging hospital psychiatrists, general practitioners, and allied services to share in the evaluation of individual cases. That this change in emphasis was real is shown in a comparison with the other two teams in regard to admissions, transfers, treatment, and frequency and type of contact between staff and patient and within staff.
Modeling Variability of Plasma Conditions in the Io Torus

Telescopic observations an in situ measurements of the Io plasma torus show the density, temperature and composition to vary over time, sometimes up to a factor of 2. While previous models of the physical and chemical processes in the Io plasma torus have reasonably modeled the conditions of the Voyager 1 era, their authors have not addressed the observed variability nor explored the sensitivity of torus conditions to input parameters. In this paper we present a homogeneous torus model parameterized by five variables (transport timescale, neutral source strength, ratio of oxygen sulfur to atoms in the source, fraction of superthermal electrons, temperature of these hot electrons). The model incorporates the most recent data for ionization, recombination, charge exchange and radiative energy losses for the major torus species (S, S(sup +), S(sup ++), S(sup +++), O, O(sup +), O(sup ++). We solve equations of conservation of mass and energy to find equilibrium conditions for a set of input parameters. We compare model plasma conditions with those observed by Voyager 1 Voyager 2, and Cassini. Furthermore, we explore the sensitivity of torus conditions to each parameter. We find that (1) torus conditions are distinctly different for the Voyager 1, Voyager 2 and Cassini eras, (2) unique torus input parameters for any given era are poorly constrained given the wide range of solution space that is consistent with the range of observed torus conditions, (3) ion composition is highly sensitive to the specification of a non-thermal electron distribution, (4) neutral O/S source ratio is highly variable with model values ranging between 1.7 for Cassini to 4.0 for Voyager 1 conditions, (5) transport times range between 23 days for Voyager 2 to 50 days for Voyager 1 and Cassini, (6) neutral source strengths range between 7 to 30 x 10(sup -4) cm (sup -3) s(sup -1) which corresponds to a net production of 0.4 to 1.3 tons/s for a torus volume of 1.4 x 10(sup 31) cm(sup 3), or 38 R(sub j)(sup 3).
Is Industrial Electronic Technique Different

With the reduction in production of military electronic equipment it is logical for radio engineers to consider entering the field of industrial electronics. This junior branch of the industry differs from communication work especially in the emphasis on costs and the type of personnel available for operation and routine servicing. The range of industrial electronics extends from standard communication equipment at one end to the large pumped ignitron and multianode tanks capable of rectifying thousands of kilowatts.
Reversal of ongoing proteinuria in autoimmune mice by treatment with C-reactive protein.

Objective To examine the ability of injection of C-reactive protein (CRP) to treat systemic lupus erythematosus (SLE) in the (NZB × NZW)F1 (NZB/NZW) mouse and to use a nephrotoxic nephritis (NTN) model to further examine the mechanism of this activity. Methods NZB/NZW mice were given a single injection of 200 μg of CRP prior to disease onset or after the onset of high-grade proteinuria. Mice were monitored weekly for proteinuria and monthly for anti–double-stranded DNA (anti-dsDNA) antibodies. NTN was induced by immunization with rabbit IgG followed by rabbit anti-mouse glomerular basement membrane. Proteinuria was measured daily, and renal pathology was scored. CRP was injected at the time of disease induction or 9 days later. Results Treatment of NZB/NZW mice with CRP prior to disease onset delayed the onset of high-grade proteinuria by 16 weeks (P < 0.0001) and prolonged survival by 13 weeks (P < 0.002). CRP treatment of NZB/NZW mice during acute disease rapidly decreased proteinuria, and the treated mice remained aproteinuric for at least 10 weeks. Control and CRP-treated mice developed similar levels of anti-dsDNA. In C57BL/6 mice, injection of CRP either before or after induction of NTN suppressed proteinuria and glomerular pathology. CRP was completely ineffective in treating NTN in interleukin-10 (IL-10)–deficient mice. Conclusion CRP injection suppresses inflammation in the kidney in SLE and NTN. The requirement for IL-10 in this protection suggests that CRP must rapidly initiate an IL-10–dependent antiinflammatory process. These findings suggest that a major function of CRP during the acute-phase response is to limit tissue damage and modulate acute inflammation.
Menin-mediated Caspase 8 Expression in Suppressing Multiple Endocrine Neoplasia Type 1

Multiple endocrine neoplasia type 1 (MEN1) is a familial tumor syndrome linked to mutation of the MEN1 gene, which encodes a tumor suppressor, menin. We previously reported that menin up-regulates the caspase 8 expression and promotes TNF-α-induced apoptosis. However, it remains unclear how menin up-regulates caspase 8 expression and whether menin-mediated caspase 8 expression plays a role in repressing MEN1 development. Here we show that menin binds the 5′-untranslated region (5′-UTR) of the Caspase 8 locus in vivo and activates transcription of a reporter gene through the 5′-UTR. Menin directly binds the 5′-UTR in a sequence-independent manner in vitro. Moreover, Men1 ablation in cells reduces acetylation of histones H3 and H4 at the 5′-UTR of the caspase 8 locus bound by menin in vivo. Notably, the MEN1-derived menin point mutants lose their ability to bind the caspase 8 locus and fail to induce caspase 8 expression and TNF-α-mediated apoptosis. Consistent with these observations, the expression level of caspase 8 is markedly reduced in insulinomas from Men1+/– mice. Together, our results indicate that menin enhances the caspase 8 expression by binding the caspase 8 locus, and suggest that menin suppresses MEN1 tumorigenesis, at least in part, by up-regulating caspase 8 expression.
The role of visioning in the pastoral counseling movement

Throughout its history, pastoral counseling has manifested a dynamic play between visioning and praxis. Frequently this interface has taken the form of “issues”, e.g., the identity issue, the theological question, the ecclesiastical relationship, and the paradigm matter. Such visioning and revisioning provide the movement with elan and should be encouraged through greater interaction with classical fields and scholars, by intensive research focused on the kinds of theological students attracted to pastoral counseling, and by stressing the importance of responsible visioning to those presently committed to the pastoral counseling movement.
Total synthesis of (±)-tricyclohexaprenol, a possible forerunner of sterols in the evolution of biomembranes

Abstract (±)-Tricyclohexaprenol ( 1 ) has been synthesized by a route involving concurrent generation of the three rings by Hg(II)-promoted conversion of 3 to 4 , and subsequent attachment of a C 10 , E,E -diene unit using the allylic silane 10 , prepared from geraniol.
Noggin signaling from Xenopus animal blastomere lineages promotes a neural fate in neighboring vegetal blastomere lineages.

In Xenopus, localized factors begin to regionalize embryonic fates prior to the inductive interactions that occur during gastrulation. We previously reported that an animal-to-vegetal signal that occurs prior to gastrulation promotes primary spinal neuron fate in vegetal equatorial (C-tier) blastomere lineages. Herein we demonstrate that maternal mRNA encoding noggin is enriched in animal tiers and at low concentrations in the C-tier, suggesting that the neural fates of C-tier blastomeres may be responsive to early signaling from their neighboring cells. In support of this hypothesis, experimental alteration of the levels of Noggin from animal equatorial (B-tier) or BMP4 from vegetal (D-tier) blastomeres significantly affects the numbers of primary spinal neurons derived from their neighboring C-tier blastomeres. These effects are duplicated in blastomere explants isolated at cleavage stages and cultured in the absence of gastrulation interactions. Co-culture with animal blastomeres enhanced the expression of zygotic neural markers in C-tier blastomere explants, whereas co-culture with vegetal blastomeres repressed them. The expression of these markers in C-tier explants was promoted when Noggin was transiently added to the culture during cleavage/morula stages, and repressed with the transient addition of BMP4. Reduction of Noggin translation in B-tier blastomeres by antisense morpholino oligonucleotides significantly reduced the efficacy of neural marker induction in C-tier explants. These experiments indicate that early anti-BMP signaling from the animal hemisphere recruits vegetal equatorial cells into the neural precursor pool prior to interactions that occur during gastrulation. Developmental Dynamics 236:171–183, 2007. © 2006 Wiley-Liss, Inc.
Probing Transient Hoogsteen Hydrogen Bonds in Canonical Duplex DNA Using NMR Relaxation Dispersion and Single-Atom Substitution

Nucleic acids transiently morph into alternative conformations that can be difficult to characterize at the atomic level by conventional methods because they exist for too little time and in too little abundance. We recently reported evidence for transient Hoogsteen (HG) base pairs in canonical B-DNA based on NMR carbon relaxation dispersion. While the carbon chemical shifts measured for the transient state were consistent with a syn orientation for the purine base, as expected for A(syn)•T(anti) and G(syn)•C(+)(anti) HG base pairing, HG type hydrogen bonding could only be inferred indirectly. Here, we develop two independent approaches for directly probing transient changes in N-H···N hydrogen bonds and apply them to the characterization of transient Hoogsteen type hydrogen bonds in canonical duplex DNA. The first approach takes advantage of the strong dependence of the imino nitrogen chemical shift on hydrogen bonding and involves measurement of R(1ρ) relaxation dispersion for the hydrogen-bond donor imino nitrogens in G and T residues. In the second approach, we assess the consequence of substituting the hydrogen-bond acceptor nitrogen (N7) with a carbon (C7H7) on both carbon and nitrogen relaxation dispersion data. Together, these data allow us to obtain direct evidence for transient Hoogsteen base pairs that are stabilized by N-H···N type hydrogen bonds in canonical duplex DNA. The methods introduced here greatly expand the utility of NMR in the structural characterization of transient states in nucleic acids.
A Resolvable octaheterohelicene based on the 1,3,4,6-tetraazapentalene ring system

Abstract The fluorescent octaheterohelicene, benzo[ h ]quinolino- [1,2″l′,2′ ]imidazo[4′ ,5′ 4,5]imidazo[l,2- a ]benzo[ h ]quinoline (bd]7) , has been resolvled by radial chromatography on plates of silica to which (-)-TAPA and (+)-TAPA were covalently bound.
Spatially explicit estimates of erosion-risk indices and variable riparian buffer widths in watersheds

Strategies for protecting and restoring riparian and stream ecosystems commonly encounter uncertainties about natural processes and management practices that contribute to environmental disturbances. Improvements in management plans require landscape approaches that account for the explicit spatial distribution and variability of different land cover types that can contribute to unstable conditions. We use a spatially explicit procedure to determine erosion-risk indices and variable riparian buffer widths in watersheds. The indices are based on land cover types that can contribute to erosion either alone or collectively. Land cover information (e.g., unstable soils, immature forest stands, roads, critical slope for land failure and rain-on-snow areas) was used to estimate erosion-risk indices. Erosion-risk indices increase with greater co-occurrences of contributing land covers. The procedure was used to identify erosion-prone areas in tributary watersheds of the Beckler-Rapid River drainage (260 km2), in the State of Washington, USA. A regression analysis of the relationship between mean sediment inputs to streams and erosion-risk indices of sixteen different watersheds indicated that erosion-risk indices explained 65% of the variation associated with sediment inputs to channels. Landscape maps of erosion-risk categories, based on ranges of erosion-risk indices, allowed spatially explicit definitions of stream reach lengths susceptible to different levels of erosion. Low to high-risk categories, and reach lengths vulnerable to erosion, also permitted the identification of the distribution of channels requiring protection by variable riparian buffers widths. The applicability of the procedure to other landscapes was demonstrated by estimating erosion risk-indices and variable riparian buffer widths for watersheds in the upper Cedar River drainage near Seattle, Washington. This approach allows watershed managers to use existing records and published information to address environmental problems within highly variable landscapes.
A practical guide for solid-state NMR distance measurements in proteins

Rotational resonance (R 2 ) and rotational echo double resonance (REDOR) are powerful solid-state NMR techniques that can be applied in a site-directed fashion for precise distance measurements in proteins. These tools are well suited for systems in which a few precise distance measurements are needed to understand a mechanism or map a bind- ing site, particularly if this information is unavailable from x-ray crystallography or solution NMR, as is often the case for membrane proteins. Strategies and challenges in the design and implementation of such experiments are described and illustrated with experiments probing mechanisms of transmembrane signaling in bacterial chemotaxis receptors. ! 2007 Wiley Periodicals, Inc. Concepts Magn Reson Part A 30A: 21-39, 2007
Images of mathematicians: a new perspective on the shortage of women in mathematical careers

Though women earn nearly half of the mathematics baccalaureate degrees in the United States, they make up a much smaller percentage of those pursuing advanced degrees in mathematics and those entering mathematics-related careers. Through semi-structured interviews, this study took a qualitative look at the beliefs held by five undergraduate women mathematics students about themselves and about mathematicians. The findings of this study suggest that these women held stereotypical beliefs about mathematicians, describing them to be exceptionally intelligent, obsessed with mathematics, and socially inept. Furthermore, each of these women held the firm belief that they do not exhibit at least one of these traits, the first one being unattainable and the latter two being undesirable. The results of this study suggest that although many women are earning undergraduate degrees in mathematics, their beliefs about mathematicians may be preventing them from identifying as one and choosing to pursue mathematical careers.
Effect of chemotherapy on hepatic collagen and glycosaminoglycan metabolism in Schistosoma mansoni-infected mice

Abstract The dynamics of biosynthesis and accumulation of collagenous proteins and glycosaminoglycans (GAGs) in liver granulomas induced by eggs of Schistosoma mansoni were studied in mice following eradication of adult worms by chemotherapy. The relatively synchronous granulomas around parasite eggs were isolated from the livers at ensuing 2-week intervals; the number of recoverable granulomas per liver gradually decreased and was 7% of initial values at 20 weeks. Hepatic or granuloma-associated extracellular matrix components increased for 4 weeks after treatment despite cessation of ova deposition. At 12 weeks after chemotherapy the rate of GAG biosynthesis per total liver granuloma fraction, measured by 3 H-glucosamine incorporation, decreased dramatically; this was followed by a decrease in the amount of GAGs present. The rate of collagen biosynthesis per total liver granuloma fraction, measured by 3 H-proline incorporation, began to decline at 14 weeks and a decrease in the amount of collagen present was noted at 16 weeks. Our results demonstrated that liver granulomas induced by S. mansoni eggs synthesize collagens and GAGs for about 4–6 weeks following parasitological cure. The subsequent resolution of granulomas proceeds first by a reduction in GAG biosynthesis followed 4–8 weeks later by decreased collagen biosynthesis, followed by accelerated resolution of both collagen and GAGs.
Flow slides and the undrained brittleness index of some mine tailings

Abstract This paper discusses material parameters related to flow slides in saturated mine tailings embankments. Several studies of tailings embankment failures indicated that the failures took place very quickly and were characterized by extensive toe disturbance - both features typify flow slides in granular soils which are associated with large pore pressures and reduced (residual) shear strength. The brittleness index proposed by Bishop (1967, 1973) has been shown to relate postrupture behaviour of slopes to the peak and residual strength parameters of soils. In this study the undrained brittleness index was determined from stress-controlled isotropically consolidated undrained triaxial tests on tailings from three mining operations which produced garnet, iron ore and zinc. Test variables that influenced the brittleness index and thus peak and residual shear parameters included varying initial (before consolidation) void ratio, i.e., as placed relative density, and consolidation pressure. It was found that the initial void ratio was the most important parameter governing the undrained brittleness index. At a given initial void ratio the brittleness index generally increased with increasing consolidation pressures but the magnitude of this effect varied with the type of tailings. For the three types of tailings tested, it was found that when the initial dry unit weight was less than 70–75% of the maximum dry unit weight obtained from the modified Proctor test (ASTM D-1557), the undrained brittleness index was greater than 50% and further reduction in the initial dry unit weight had little effect on the index. However, the index decreased sharply to zero for all tailings over the range of consolidation pressures used when the initial percent dry unit weight increased from 75% to about 80%. This indicates that for the tailings tested and over the range of variables (initial unit weight and consolidation pressure) considered, the possibility of a flow slide due to a static load would be precluded if the initial compaction exceeded 80% of maximum.
The production and fate of phytoplankton size fractions in the plume of the Hudson River, New York Bight1

Seasonal effects of water column stability, phytoplankton growth, and copepod grazing on the biomass of phytoplankton size fractions are described in the context of variations in particulate organic carbon (POC). Net plankton biomass was more variable in time (between weeks and months), while nanoplankton biomass was more variable in space (between surface and bottom layers and between stations). Biomass was highest and most uniformly distributed during February-IMarch when net plankton diatoms dominated and doubling times approximated the flushing time of the plume. Biomass declined rapidly with depth and distance from the mouth of the estuary during June-July when nanoplankton dominated and doubling times were short relative to the flushing time of the plume. Variations in POC were well correlated with phytoplankton biomass when net plankton dominated and biomass was limited by sinking and mixing. When nanoplankton dominated, biomass was limited mainly by grazing and correlations between POC and biomass were poor. It appears that most of the biomass produced by net plankton diatoms sinks from the surface layer before the summer thermocline develops, while most of the biomass produced by nanoplankton during the summer enters pelagic food chains before sinking from the surface layer,
In vivo labelling of extractable iodotyrosines in serum of rat and dog.

SummaryExtraction was made of the protein fraction, Fraction 1, (after passage through a Sephadex G-25 column) of serum of rats fed 125-1 for 50-57 days. The presence of labelled iodotyrosines, 11-13% of the organic labelled iodine, was established. In dogs injected once with 125-1, 12-18% of total serum radioactivity was extractable as iodotyrosines by 12 hours after labelling. In man, iodotyrosines in serum were not found to be labelled, with one possible exception.
Application of Multidimensional Utility Theory in Determining Optimal Test-Treatment Strategies for Streptococcal Sore Throat and Rheumatic Fever

In medical decision making one must usually deal with a number of objectives, many of which conflict, under conditions of uncertainty. Multidimensional utility theory offers a methodology for dealing with such situations. This paper describes the analysis of a medical problem, the determination of optimal test and treatment strategies for streptococcal sore throat and rheumatic fever, in which the formulation and assessment of a multidimensional utility function were a central part. We determine optimal diagnostic and treatment strategies, comment on the usefulness of the procedure, and summarize some potential applications.
Intellectual, Motor, and Language Sequelae Following Closed Head Injury in Infants and Preschoolers

Examined cognitive and motor performance during the subacute stage of recovery and 8 months postinjury in 21 infants and preschoolers who sustained a closed head injury (CHI). Children sustaining severe CHI, who exhibited impaired consciousness for at least 1 day, were impaired on measures of intelligence, motor, expressive language, and receptive language functions on the baseline and follow-up evaluations relative to children with mild-moderate injuries. Irrespective of injury severity, motor and expressive language functions were the most vulnerable to the effects of CHI. Results are discussed in terms of the rate of development of cognitive functions.
Development of Nanostructures in Thermoelectric Pb-Te-Sb Alloys

In analogy to recent demonstrations of enhanced thermoelectric properties in superlattice materials, composite structures with nanoscale features promise dramatic improvements in the figure of merit of thermoelectric materials. Fabrication of nanostructured thermoelectric materials via bulk synthesis is an attractive route for commercial applications. Nanometer scale lamellae of PbTe and Sb2 Te3 form when quenched eutectic PbTe-Sb2Te 3 melt is subsequently annealed. The lamellar spacing depends on the temperature and time of the anneal. The mechanism for the development of the nanostructures can be characterized by examining the fraction of material transformed as a function of anneal time. Preliminary analysis of the shape factor exponent reveals that the evolution of the nanostructured lamellae is likened to the thickening of very large plates. The coarsening of the lamellar spacing is also examined as a function of time
Creating incentives for accountability in patient care.

When looking at incentive and payment systems, what behavior is being incentivized must be considered.