cssi/SciSciGPT-SciSciNet huggingface dataset:
Induction of inflammatory bowel disease accelerates adenoma formation in Min +/- mice.

Background The accelerated incidence of colorectal carcinoma in individuals with inflammatory bowel disease suggests that cellular perturbation triggered by chronic inflammation is linked to the development of dysplasia and neoplastic transformation. To test the mechanistic links between these processes, we employed the following murine strains: (1) multiple intestinal neoplasia (Min) +/− mice, bearing a mutation in the adenomatous polyposis coli (APC) gene; (2) mice deficient in interleukin 10 (IL-10), which normally develop enterocolitis; and (3) Min +/−/IL-10 null mice, first developed in our laboratory. Methods Mice with either parental strain or the cross were sacrificed at time points ranging from 10 to 30 weeks of age. The small bowel and colon of 170 IL-10 null mice, 31 Min +/− mice, and 120 Min +/−/IL-10 null mice were examined microscopically. Results The number of flat adenomas was increased in the colons of the Min +/−/IL-10−/− mice, compared with the Min +/− mice (P = .0005). Neither colitis-type dysplasia nor carcinoma was increased in the Min +/−/IL-10 −/−, compared with the IL-10 null mice (P = .18). Mice deficient in IL-10 developed colitic-type dysplasia (P = .0001) or carcinoma (P = .0001) correlated with increasing inflammation. Conclusions Breeding the Min +/− genotype into the IL-10 −/− background increased the incidence of colonic adenomas. Our studies demonstrate that acceleration of dysplasia and progression to invasion were associated with the degree of the inflammatory response in mice deficient in IL-10. These findings provide a novel system to dissect the pathways by which inflammatory mechanisms accelerate adenoma formation.
Vanadosilicate mesoporous SBA-15 molecular sieves incorporated with N-alkylphenothiazines

Mesoporous silica SBA-15 molecular sieves have been incorporated with various amounts of vanadium via incipient-wetness impregnation with vanadium oxide triisopropoxide in hexane followed by calcination. The products (VSBA-15) have been characterized by nitrogen adsorption and diffuse reflectance UV-visible and electron spin resonance spectroscopies. The results show that the vanadium exists as isolated tetrahedral V 5+ ions in dehydrated VSBA-15 with Si/V ≥ 40 while vanadium chains develop as vanadium loading increases. Upon hydration a large fraction of the vanadium is transformed to square pyramidal and distorted octahedral V 5+ ions by additional coordination to water molecules, suggesting an interior wall surface location for these V 5+ ions. Upon CO reduction or incorporation of N-alkylphenothiazines (PC n ), part of the V 5+ is reduced to vanadyl VO 2+ ions. While incorporation of PC n into VSBA-15 in the dark generates some PC n + cation radicals, ultraviolet photoionization at room temperature further increases the yield for Si/V = 80 and 40. The PC n + radicals are more stable in VSBA-15 than in siliceous SBA-15, and the photoyield increases with vanadium loading. The photoyield and stability of PC n + also increase with increasing alkyl chain length of the N-alkylphenothiazines.
Conflict Between Nursing Home Staff and Residents’ Families Does It Increase Burnout?

Objective: In this study, the authors examine the influence of conflict between nursing home staff and family members of residents on staff burnout. Method: Data were collected from interviews with a representative sample of 655 nursing home nurses and nursing assistants. Hypotheses were tested using structural equation modeling. Results: Results indicate that conflict with family members increases staff burnout and decreases staff satisfaction. Staff and family conflict increases when staff members feel they do not have enough time to complete required tasks. Level of conflict decreases when staff perceive that family members have care expectations that are similar to their own. Interestingly, staff who have personal experience as family caregivers are more likely to report conflict with family members of residents, a result that necessitates further study. Discussion: Staff burnout and dissatisfaction affects both individuals and organizations. Policy that addresses staff and family interaction can have...
Immunochemical comparison of mutant glucocorticoid receptors and wild type receptor fragments produced by neutrophil elastase and chymotrypsin.

Abstract We characterized the glucocorticoid receptor fragments produced by neutrophil elastase and compared these receptor fragments to nuclear transfer increased (nt i ) mutant receptors. Neutrophil elastase and chymotrypsin digested [ 3 H]dexamethasone 21-mesylate labeled receptors at different sites to produce 52 kDa and 42 kDa fragments respectively. Both the 52 kDa elastolytic receptor fragments and 42kDa chymotryptic receptor fragments bound to DNA-cellulose and were immunoadsorbed by anti-glucocorticoid receptor monoclonal antibodies (BUGR2). More extensive digestion of labeled receptors by neutrophil elastase produced 29 kDa receptor fragments that did not bind to DNA-cellulose and did not react with BUGR2 antibodies The size of nt i mutant receptors from S49 mouse lymphoma cell variants is intermediate between that of the 52 kDa elastolytic receptor fragments and 42 kDa chymotryptic receptor fragments. The nt i receptors bound to DNA-cellulose with the same affinity as the 52 kDa elastolytic receptor fragments. However, the nt i receptors were not immunoadsorbed by BUGR2 antibodies and did not react with these antibodies on Western blot analysis of denatured cellular proteins. The results indicate that 52 kDa elastolytic receptor fragments, 42 kDa chymotryptic receptor fragments and nt i mutant receptors correspond to the same region of the receptor molecule. The failure of nt i receptors to react with BUGR2 antibodies suggests that the nt i receptors may have an altered sequence compared to the corresponding region of normal receptors.
A self-propelled colonoscope: Aer-O-Scope

Screening for colorectal cancer by full colon imaging has major advantages for detection of precancerous polyps. Colonoscopy is not feasible in all settings and is undesirable in some because of its cost, risk, need for sedation, and limited capacity. The Aer-O-Scope (GI View Ltd.; Ramat Gan, Israel) is a self-propelled, diagnosis-only colonoscope. Its propulsion system utilizes two balloons, one inflated and fixed in position in the rectum and a second, mobile balloon with a capsule endoscope fixed to the advancing end and a supply cable trailing from the opposite end. Gas insufflated between the balloons advances the mobile balloon. Propulsion has proven effective in pig and human colons in small studies. The imaging capsule has a forward viewing lens with a 90° angle of view and an “Omni” lens with 360° circumferential vision, including 25° of both forward vision and retrovision. The imaging system has proven effective in both in vivo and in vitro porcine models.
Gastric exocrine and endocrine secretion.

Purpose of reviewThis review summarizes the last year's literature regarding the regulation and measurement of gastric exocrine and endocrine secretion.Recent findingsParietal cells, distributed along much of the length of the oxyntic glands, with highest density in the neck and base, secrete HCl as
Modeling DSC Annealing Peaks for Polyetherimide: Incorporation of Temperature Gradients

Enthalpy recovery of polyetherimide is measured during heating with differential scanning calorimetry (DSC) after cooling at various rates. The resulting annealing peaks are fit using the Moynihan-Tool-Narayanaswamy model of structural recovery. A self-consistent phenomenological equation is used to describe the experimentally observed structure and temperature dependence of the relaxation time in both glass and equilibrium regimes. Temperature gradients in the DSC sample are incorporated into the model calculations. When no thermal gradients are assumed, model parameters are found to vary with thermal history despite the use of the self-consistent equation for the relaxation time. Accounting for the presence of thermal gradients in the DSC sample is found to affect the values of the model parameters needed to fit the data. However, thermal gradients are unable to account for the thermal history dependence of the model parameters or for the discrepancy between the observed and calculated shapes of the DSC annealing peaks.
Intraperitoneal Therapy Administered through a Groshong Catheter

This report describes a new device for delivery of intraperitoneal therapy. From October 1989 through March 1991, 27 externally accessed Groshong (Bard Access Systems, UT) catheters were placed transabdominally into 24 patients with presumed epithelial ovarian cancer at the conclusion of primary or second-look laparotomy. Total duration of catheter use was 81 months (range, 1-62 weeks). Fifty-seven cycles of intraperitoneal therapy were administered through 18 catheters (range, 1-11). Nine catheters were removed without being used after patients randomized off intraperitoneal treatment arms or were ineligible for intraperitoneal protocols. There were no complications associated with catheter placement or removal. None of the catheters became obstructed or dislodged while in place. There were no cases of infectious peritonitis, although one patient developed an exit-site skin infection. Surgery is not required to remove the Groshong catheter which fosters empiric placement of the device at the time of laparotomy in all patients potentially eligible for intraperitoneal therapy. The device-related infection rate of 4.2 per 100 patients is similar to that described using other implanted devices. Catheter maintenance is easy and patient acceptance is good. The Groshong catheter is a safe, reliable, and acceptable means of delivering intraperitoneal therapy.
A career in motion: from the back office to the executive office

Some organizations particularly companies that create new technologies may have a CTO and a CIO. In that case, the CTO is generally responsible for overseeing the technologies that the company creates, and the CIO is responsible for applying information technologies to the organization. The priorities of the position can be somewhat defined by the organizational unit to which they report. The reporting line is between the CIO and the CFO, it can be because the CIO function is viewed as a cost that needs to be managed and controlled. As a result, it is important to a CIO to have people in the IT organization who are both competent and comfortable to express their opinion about what should be done
Differential effects of zinc on hyperpolarizing and depolarizing GABAA synaptic potentials in hippocampal slice cultures

Abstract We have examined the changes in GABA A -mediated synaptic potentials recorded from CA3 pyramidal neurons in hippocampal slice cultures following application of zinc (Zn 2+ ). Unlike 4-AP, Zn 2+ did not enhance fast hyperpolarizing potentials but primarily enhanced depolarizing GABA A potentials. Zn 2+ did not alter the postsynaptic response of pyramidal neurons to pressure applied GABA, consistent with previous reports that Zn 2+ enhances the release of GABA from presynaptic terminals. To examine the role of local circuitry in the production of Zn 2+ responses, we recorded from cultures maintained for 7–10 days following removal of the dentate and hilus to allow complete degeneration of the mossy fibers (DGX cultures). Zn 2+ produced giant depolarizing potentials (GDPs) in DGX cultures that were identical to those in intact cultures. In contrast, the 4-AP response was dramatically altered in DGX cultures. In DGX cultures, Zn 2+ co-applied with 4-AP appeared to inhibit the production of fast hyperpolarizing GABA A synaptic potentials produced by 4-AP alone. This inhibition of fast hyperpolarizing potentials suggests that Zn 2+ may reduce the release of GABA onto pyramidal cell somata. These observations suggest that Zn 2+ enhances GABA release from local circuit neurons that synapse onto pyramidal cell dendrites, and inhibits GABA release onto pyramidal cell somata.
Cells of the oligodendrocyte lineage proliferate following cortical stab wounds: An in vitro analysis

We have previously shown that a cortical stab wound induces the proliferation of microglia and astrocytes in situ, but no evidence was obtained for proliferation of cells of the oligodendrocyte lineage (Amat et al., 1996). To study further the properties of cells involved in repair following brain injury, groups of adult rats received either sham operations or bilateral stab wounds. Proliferating cells were labeled in vivo 3 days later with [ 3 H]-thymidine (Thy) and sacrificed the same day. Oligodendrocyte-enriched preparations were isolated, cultured, and analyzed. The fate and antigenic phenotype of the proliferating cells was analyzed using three-color immunofluorescence combined with autoradiography at 1, 2, 3, 5, and 10 days in vitro (DIV). Cells were immunostained for ganglioside GD3 (glial stem cells), 04 antigen (cells of the oligodendrocyte lineage), galactosyl ceramide (GC, differentiated oligodendrocytes), and GFAP (astrocytes). Thymidine-labeled O4+/GC- cells were found only in cultures from wounded animals and most of them differentiated in vitro as mature oligodendrocytes, but no Thy+/O4+/GC+ oligodendrocytes were seen at 1, 2, or 3 DIV. There was also a marked increase in the number of Thy+/GD3+ cells in the experimental cultures. In both experimental and control groups the total number of Thy+ and Thy- GD3+ cells declined with time in culture concomitant with an increase in total number of both Thy+ and Thy- GFAP+ astrocytes, and without any significant change in the Thy+ cell fraction of O4+ oligodendrocytes in the experimental cultures. Therefore most of the GD3+/O4- cells apparently differentiated as GFAP+ astrocytes, not as oligodendrocytes. We conclude that O4+/GC- oligodendrocyte precursor cells, but not differentiated oligodendrocytes, proliferate in response to brain injury. These cells proliferate slowly or not at all in normal adult animals and constitute a phenotypically and kinetically distinct group from the GD3+ glial precursors. This result is consistent with the existence within the adult CNS of a quiescent premyelinating oligodendrocyte. We propose that these immature committed oligodendrocytes are induced to proliferate at the wound site and serve as a source of new oligodendrocytes.
An analysis of the impact of climate change on crop yields and yield variability

This paper develops an econometric model of stochastic production functions to quantify the impacts of climatic variables on the mean, variance, and covariance of crop yields. The estimates of the production function parameters and their elasticities are utilized to analyse the impacts of the projected climate change on agriculture. The results show that the climate change will have modest effects on the mean crop yields, but will significantly reduce the variance and covariance for most of the crops considered. The results have implications for allocations of agricultural land among crops and for crop production mix.
Sugar, Sex, and TGF-β in Diabetic Nephropathy

TGF-β is well known to play a critical role in diabetic kidney disease, and ongoing clinical studies are testing the potential therapeutic promise of inhibiting TGF-β production and action. An aspect of TGF-β action that has not received much attention is its potential role in explaining sex-related proclivity for kidney disease. In this review, we discuss recent studies linking TGF-β signaling to sex-related effects in diabetic kidney disease and suggest targets for future studies.
Seeded Growth of Monodisperse Gold Nanorods Using Bromide-Free Surfactant Mixtures

We demonstrate for the first time that monodisperse gold nanorods (NRs) with broadly tunable dimensions and longitudinal surface plasmon resonances can be synthesized using a bromide-free surfactant mixture composed of alkyltrimethylammonium chloride and sodium oleate. It is found that uniform gold NRs can be obtained even with an iodide concentration approaching 100 μM in the growth solution. In contrast to conventional wisdom, our results provide conclusive evidence that neither bromide as the surfactant counterion nor a high concentration of bromide ions in the growth solution is essential for gold NR formation. Correlated electron microscopy study of three-dimensional structures of gold NRs reveals a previously unprecedented octagonal prismatic structure enclosed predominantly by high index {310} crystal planes. These findings should have profound implications for a comprehensive mechanistic understanding of seeded growth of anisotropic metal nanocrystals.
An assessment of some criticisms of goal programming

Abstract Goal programming (GP) has proven to be a topic of much controversy in this journal. The intent of this paper is to examine some of the characteristics of goal programming that have engendered this controversy and to assess the severity of the associated shortcomings. Also, an effort is made to identify the conditions under which the use of GP is most theoretically defensible.
Implicit Solitary Wave Solutions of the Generalized Magma Equation

Abstract The generalized magma equation, in which dispersion and nonlinearity are coupled together in a manner reminiscent of the Harry-Dym equation, is solved to indicate both periodic and aperiodic implicit solitary wave solutions. It is argued that the presence of an additional spatial derivative in the magma equation also permits explicit solitary wave solutions, a feature not shared by the Harry-Dym equation.
The Rhetoric of Translation: Three Early Perspectives on Translating Torah

Three of the earliest extant Jewish exegetes, Aristobulus, Aristeas, and Philo, all state that King Ptolemy was responsible for a Greek translation of the Hebrew sacred writings. Scholarly discussion has focused on finding the historical kernel in these stories, or linking their creation to a particular event such as the official promulgation of an original or corrected Greek translation. The Letter of Aristeas is usually considered the most accurate version, in large part because it later was used as an introduction to the Septuagint. These discussions have overlooked the fact that in each case the basic plot is fine-tuned to suit each exegete's own ideas about how the Torah was written, how the text and its translation should be read and interpreted, and by whom. A comparison of the three versions reveals that each writer embellishes this bare-bones plot in a distinct manner. In particular, “historical” details are created by each writer that support the very exegetical endeavor he is undertaking. The story of the translation becomes a vehicle for creating all the components necessary to justify the exegete's role, from the creation of a unitary “Torah” out of the multiplicity of versions and stories to the motivation for the particular interpretative moves “demanded” by the very qualities of this Torah. Comparing the three stories gives us valuable insights into the self-perceptions of the exegetes and the emergence of what will become a standard model of text-author-exegete in Judaism.
Enthalpies of dilution and relative apparent molar enthalpies of aqueous sodium sulfite at 298.15 K

Abstract Enthalpies of dilution of aqueous Na 2 SO 3 at 298.15 K were measured by solution calorimetry, with special care to exclude oxygen during measurements. Relative apparent molar enthalpies L φ were evaluated from the results.
Expression of HNF4α variants in pancreatic islets and Ins‐1 β cells

Background Hepatocyte nuclear factor (HNF4alpha) is a nuclear receptor essential for endodermal differentiation and cell functions in the adult pancreas, liver, and other tissues. Mutations in the HNF4A gene cause MODY1. Up to nine protein variants arise from two developmentally regulated promoters. Because some variants lack the N-terminal activation function 1 (AF-1) and/or C-terminal inhibitory F domain, defining their tissue-specific regulation and function is important for understanding pancreatic beta cell behaviour. Methods Expression of HNF4alpha variants in islets, rat Ins-1 insulinoma cells, and human Hep3B hepatocellular carcinoma cells was assessed using a long-range reverse transcription-polymerase chain reaction (RT-PCR) strategy capable of recognizing each combination of mRNA termini. Protein expression was verified by immuno-blotting with terminus-specific antibodies and DNA-binding assays. Results Mouse islets and both cell lines express HNF4alpha9, which lacks both AF-1 and the F domain. Islets also expressed the HNF4alpha P1 promoter variants HNF4alpha1/alpha2, and Hep3B cells expressed HNF4alpha3. When ectopically expressed in COS-7 cells, HNF4alpha1, alpha3, alpha7, and alpha9 each stimulated an HNF4alpha-dependent promoter. Variants containing exon 1B (HNF4alpha4 - alpha6) were not detected. Lack of canonical splicing signals and species conservation argues against exon 1B usage. Conclusions This is the first report of HNF4alpha9 expression in any tissue. Our findings extend our understanding of HNF4alpha gene transcription and function. This knowledge may be useful in efforts to recover or establish regulated insulin secretion.
The political impact of foreign labor: a re-evaluation of the Western European experience.

Foreign workers in Western Europe generally have been portrayed as powerless and voiceless. Especially for contemporary Marxists, foreign labor policy is seen as serving to reinforce the political status quo. This article suggests that foreign workers in Western Europe participate politically more often and in more diverse ways than generally thought. Their participation often is politically disruptive and has contributed to the growing perception that the sociopolitical costs of foreign labor policy outweigh its economic benefits.
Quantifying stochastic resonance in bistable systems: Response vs residence-time distribution functions

A wealth of research on stochastic resonance (SR) during the past decade has led to different ways of defining this phenomenon. Most prominent are measures based on the response function and on the residence-time distribution function. While the theory for the response functions is well developed, a first fully systematic theory for the residence-time distribution functions is developed in this paper. Subsequently we reconsider formerly introduced measures of SR based on the residence-time distribution and compare with those based on the response function.
A pilot model in two dimensions for conformally invariant particle theory

Abstract The two-dimensional analog of the mathematical model for elementary particles treated in this journal vol 75, 1–57, is developed with greater explicitness than in the four-dimensional case, preliminary to quantization. In Part I the section space of the complex spannor bundle is studied. Invariant subspaces, invariant forms, and irreducible positive-energy factors under the connected conformal group are determined; transformation properties under discrete symmetries are also treated. Relations to the spinor bundle are treated; the Dirac operator is a canonical transform of the quadratic Casimir on the spannor bundle, and the section spaces have the same invariant factors; at the same time, the spinors constitute a deformation of the spannors. Two natural parallelizations of the spannor bundle and their intertwining operator are computed. The irreducible factors of the spannor section space under the conformal group are determined by their restrictions to Minkowski space, and this group acts continuously in the L2-topology, in contrast to its action on the spinor section space.
Surface tension-driven self-folding polyhedra.

We discuss finite element simulations and experiments involving the surface tension-driven self-folding of patterned polyhedra. Two-dimensional (2D) photolithographically patterned templates folded spontaneously when solder hinges between adjacent faces were liquefied. Minimization of interfacial free energy of the molten solder with the surrounding fluidic medium caused the solder to ball up, resulting in a torque that rotated adjacent faces and drove folding. The simulations indicate that the folding process can be precisely controlled, has fault tolerance, and can be used to fold polyhedra composed of a variety of materials, ranging in size from the millimeter scale down to the nanometer scale. Experimentally, we have folded metallic, arbitrarily patterned polyhedra ranging in size from 2 mm to 15 μm.
Effect of Salinity on the Temperature Preference and Tolerance of Age‐0 Mayan Cichlids

Abstract We measured the salinity tolerance, temperature tolerance, and preferred temperature of the Mayan cichlid Cichlasoma urophthalmus to determine if temperature and salinity would limit the range expansion of this introduced species in Florida. Salinity tolerance at 25°C exceeded 37‰. The upper and lower ultimate lethal temperatures in freshwater were 39 and 15°C, respectively. Acclimation to 15‰ salinity had no effect on the lower incipient lethal temperature (15°C). Thermal preference determined in a horizontal temperature gradient was 32.8°C in freshwater, 39.2°C at 15‰, and 26.9°C at 30‰ salinity. Our results indicated that temperature and salinity are not likely to limit range expansion of the Mayan cichlid from its present location in the southern portion of the Everglades National Park, but that the species' spread may be blocked by cold winter temperatures in north Florida.
Stimulation of bile acid synthesis by dibutyryl cyclic AMP in isolated rat hepatocytes.

Freshly isolated rat hepatocytes were used to examine the effects of dibutyryl cyclic AMP on the incorporation of14C-acetate and14C-cholesterol into bile acids. After an initial lag period, both precursors were incorporated into cholic and chenodeoxycholic acids at a linear rate for the subsequent 60 min. An apparent stimulation of bile acid formation from14C-acetate by dibutyryl cyclic AMP was complicated by the concomitant inhibition of cholesterol synthesis. In experiments with14C-cholesterol, dibutyryl cyclic AMP (1 mM) increased the labeled cholic and chenodeoxycholic acids in the medium by 83 and 224%, respectively, but cellular levels of labeled bile acids were unchanged. As a result, the nucleotide stimulated the overall incorporation of14C-cholesterol into cholic acid by 39% and into chenodeoxycholic acid by 123%. The mean ratio of labeled cholic to chenodeoxycholic acid declined from 55∶45 in control cells to 41∶59 in cells incubated with dibutyryl cyclic AMP. The results demonstrate that label incorporation can be used to study the regulation of bile acid synthesis in isolated hepatocytes. We propose that dibutyryl cyclic AMP enhances bile acid production by phosphorylating, and thus stimulating the activity of, cholesterol 7α-hydroxylase, the rate-limiting enzyme in bile acid synthesis.
Determination of trace element concentrations in meteorites by inductively coupled plasma — Mass spectromety

Determination of 25 trace elements in the meteorites Allende and Murchison by ICP-MS is described. Samples are digested using HF, HNO3, and HClO4 at 140°C and diluted into HNO3. Element concentrations were determined using USGS terrestrial rocks as standards for calibration. Precision and accuracy of the technique, evaluated based on measurements of samples of known composition, are for 16 elements better than 10%.
Effect of Localized Metal Matrix Composite Formation on Spot Friction Welding Joint Strength

In this study, metal particles were added during the spot friction welding (SFW) process, a solid state sheet metal joining process, to create a localized metal matrix composite (MMC)for the improvement of lap shear strength in AISI6111-T4 aluminum alloy sheets. The Ancorsteel ® 1000 particles were compressed between the upper and lower sheets and distributed concentrically around the tool axis perpendicular to the plate surface, which formed a localized MMC and were effective as the reinforcement particles in aluminum 6111 -T4 alloy sheets. Results revealed that the MMC reinforcement improved the lap shear strength of SFW joints by about 25%. An aluminum-ferrous solid solution was formed around the steel particles along the aluminum matrix interface. The load-deflection curve shows that the steel particle MMC increased both the strength and ductility of SFW joint. This is attributed to two phenomena observed on the failed lap shear tensile specimens with SFW MMC. One is the longer and more torturous crack path, and the other is the secondary crack on steel particle MMC reinforced SFW joints.
Diethylpyrocarbonate Labeling for the Structural Analysis of Proteins: Label Scrambling in Solution and How to Avoid It

Covalent labeling along with mass spectrometry is a method that is increasingly used to study protein structure. Recently, it has been shown that diethylpyrocarbonate (DEPC) is a powerful labeling reagent because it can modify up to 30% of the residues in the average protein, including the N-terminus, His, Lys, Tyr, Ser, Thr, and Cys residues. We recently discovered, however, that Cys residues that form disulfide bonds appear to be modified by DEPC as well. In this work, we demonstrate that disulfide linked Cys residues are not actually reactive with DEPC but, instead, once reduced, free Cys residues can capture a carbethoxy group from other modified amino acids via a solution-phase reaction that can occur during the protein digestion step. This “scrambling” of carbethoxy groups decreases the amount of modification observed at other residues and can potentially provide incorrect protein structural information. Fortunately, label scrambling can be completely avoided by alkylating the free thiols after disulfide reduction.
Regulation of progesterone signaling during pregnancy: implications for the use of progestins for the prevention of preterm birth.

Abstract Preterm birth is a major cause of neonatal morbidity and mortality. Progesterone plays a critical role in suppressing the inflammatory signals that would induce parturition prior to term. Progesterone signaling is regulated in a variety of ways during pregnancy. Endocrine production of high levels of progesterone by the placenta ensures the availability of high levels of progesterone throughout pregnancy. Paracrine regulation of progesterone metabolism in target tissues, particularly the myometrium and cervix, also determines the amount of progesterone ligand available. Progesterone metabolism can also lead to the formation of metabolites that contribute to its effects. In particular, 5β-dihydroprogesterone formation by aldo-keto reductase 1D1 appears to play an important role in maintaining uterine quiescence. Progesterone signaling can also be regulated at the receptor level through changes in the relative expression of the nuclear progesterone receptor isoforms, reduced expression of membrane receptors, and changes in the expression levels of coactivators and/or corepressors, including nuclear factor κB. Progesterone and 17α-hydroxyprogesterone caproate (17OH-PC) have recently been shown to reduce preterm births in women with previous preterm birth or shortened cervix. It is important to realize that these two progestins are likely to act in significantly different ways, which will likely influence their efficacy. The structural differences and resistance to metabolism exhibited by 17OH-PC means that it will be unable to activate some of the pathways that progesterone activates, but that it also will not be subject to paracrine inactivation. The fact that progesterone therapy works for maintaining pregnancy in some women, indicates that for those women insufficient levels of progesterone ligand in target tissues is a determining factor in early parturition, despite high levels of circulating progesterone. This article is part of a Special Issue entitled ‘Pregnancy and Steroids’.
Hell Hath No Fury Like a Graduate Waiting on Tables

In 1993, the Responsive College Unit (RCU), an independent educational market research organization based in Blackburn, was commissioned by the East Lancashire Training and Enterprise Council (ELTEC) to evaluate the labour market experiences of graduates from Lancashire. Describes the survey which followed almost 6,500 graduates; 40 per cent of the entire graduate cohorts for the period 1991‐93 returned questionnaires. Suggests that the results shed new light on the plight of graduates seeking employment in the current recession and also identified important factors which determine the extent to which local economies like Lancashire are able to retain the skills of their most qualified young people. Describes the main findings from the research and identifies the picture that emerged of the current realities of the transition from higher education to work.
The effects of water-to-alkoxide ratio on the properties of gels and sol-gel derived high T c ceramic superconductors

Type II (Y1Ba2Cu3O6+k) superconductors have been fabricated via sol-gel processing. Cu(II) ethoxide, Ba-methoxyethoxide, and Y-methoxyethoxide were synthesized from high purity metals. Gels were formed by mixing metal alkoxides, water, and solvents. The water-to-metal alkoxide ratio was chosen to be 1:1, 2:1, and 4:1 which resulted in a sol-to-gel transition time ranging from two to five days. The dried gels were fired at 950° C in flowing oxygen for 15 hrs and then slowly cooled to room temperature. The microstructure of the superconductors consisted of several phases. Susceptibility vs temperature curves showed that both the transition temperature (78 to 83 K) and the sharpness of the paramagnetic to diamagnetic transition were affected by the water-to-metal alkoxide ratio.
Stereochemistry involved in the mechanism of action of dextransucrase in the synthesis of dextran and the formation of acceptor products

Abstract A proposed sequence of events in the synthesis of dextran and in the formation of acceptor products by dextransucrase from Leuconostoc mesenteroides B-512F has been developed with molecular models. The following mechanism is postulated: (1) two nucleophiles at the active site displace fructose from two sucrose molecules, giving two β-glucosyl intermediates; (2) these two β-glucosyl units rotate together so that the C 6 -hydroxyl of each is apposed to the α-side of C 1 of the other; (3) one glucosyl unit assumes a boat conformation in which the bond to the enzyme is axial; (4) the C 6 -hydroxyl oxygen of the other glucosyl unit makes a nucleophilic attack on C 1 of the first, displacing the enzyme nucleophile and making an α-1,6 bond; (5) rotations about the new α-1,6 linkage remove the transferred glucose from the active site. The free enzyme nucleophile attacks another sucrose as in step (1), and then steps (2)–(5) are repeated as the reducing-end glucosyl unit of the growing chain assumes the boat conformation and is attacked by the C 6 -hydroxyl of the new glucosyl unit, which displaces the enzyme nucleophile and forms another α-1,6 linkage, about which rotations occur to remove the growing dextran chain from the active site. An additional feature of the mechanism presented here is a pair of enzymic proton-exchange groups, which protonate the glycosidic oxygen of sucrose to facilitate cleavage, and then remove a proton from the attacking C 6 hydroxyl during the polymerization reaction. Acceptors are polyhydroxy compounds which are capable of nucleophilic attack on enzyme-bound β-glucosyl or dextranosyl units to give α-glucosides or dextranosides. Noting the broad acceptor specificity of the enzyme and the unusual structure of some of the acceptor products, we have proposed that acceptor specificity is determined not by an enzymic binding site per se, but by the formation of hydrogen-bonded complexes between the acceptors and the glucosyl or dextranosyl enzyme intermediates. The acceptor attack on C 1 of the β-glucosyl enzyme is mediated by the same proton-exchange group as that proposed for catalysis of polymerization. It is shown that specific multiple hydrogen bonding to the glucosyl-enzyme intermediate can account for the formation of the observed acceptor products from α-methyl- d -glucoside, d -fructopyranose, isomaltose, maltose, β- d -mannopyranose, β- d -galactofuranose, cellobiose, lactose, β,β-trehalose, α,β-trehalose, and raffinose.
Extension of Tao-Mason Equation of State to Mixtures: Results for PVTx Properties of Refrigerants Fluid Mixtures

Tao and Mason (J. Chem. Phys. 1994, 100, 9075−9084) developed a statistical-mechanical-based equation of state (EOS) for pure substances. In the present study, we have successfully extended this EOS to fluid mixtures, selecting refrigerant fluid mixtures as the test systems. The considered refrigerant mixtures are R32 + R125, R32 + R134a, R134a + R152a, R125 + R143a, R125 + R134a, R32 + R227ea, R134a + R290, and R22 + R152a. The second virial coefficient, B(T), necessary for the mixture version of the Tao−Mason (TM) EOS, was determined using a two-parameter corresponding-states correlation obtained from the analysis of the speed of sound data and two constants: the enthalpy of vaporization ΔHvap and the molar density ρnb, both at the normal boiling point. Other temperature-dependent quantities, including the correction factor α(T) and van der Waals covolume b(T), were obtained from the Lennard-Jones (12−6) model potential. The cross parameters B12(T), α12(T), and b12(T), required by the EOS for mixtures, ...
Enhanced Diffusion at Intermediate Stereochemical Composition in Polypropylene by Dynamical Monte Carlo

We conduct a comprehensive study of the effect of stereochemistry on the diffusion of isotactic, atactic, and syndiotactic polypropylene (PP), with dynamical Monte Carlo. We simulate realistic two-bead Monte Carlo moves on a stereochemistry-dependent, coarse-grained model of PP based on the rotational isomeric state (RIS) model and repulsive Lennard-Jones interactions. We find that isotactic PP (iPP) diffuses faster than syndiotactic PP (sPP) as expected, but a maximum in the diffusion rate at an intermediate stereochemical composition (aPP) is also found. To determine the origin of this effect, we compare pair correlation functions of the slowest-moving beads to those of all beads, identifying conformations that limit mobility. We find a few small, long-lived clusters with chain conformations reminiscent of those in crystals in iPP and sPP; although slow-moving beads also cluster in aPP, they are short-lived with no dominant conformations. We look at the effects of local stereochemistry through Monte Car...
Intracisternal virus-like particles in brain of a multiple sclerosis patient☆

Abstract Doughnut-shaped particles, 55–65 nm in diameter, were revealed by electron microscopy in the cisterns of the rough endoplasmic reticulum of cells from an active lesion in autopsied brain tissue from a multiple sclerosis patient. The morphology of the particles closely resembled that of coronaviruses.
Experimental herpes simplex virus encephalitis: Comparative effects of treatment with cytosine arabinoside and adenine arabinoside.

Experimental herpesvirus encephalitis in weanling mice was treated with either cytosine arabinoside or adenine arabinoside to determine the comparative effectiveness of the two compounds on survival and on the concentration of virus in the brain. The uniformly fatal course of the encephalitis was not altered by any dosage of cytosine arabinoside. In contrast, treatment with adenine arabinoside resulted in long-term survival of the majority of the infected animals. The concentration of virus measured in the brains of animals treated with two different dosages of cytosine arabinoside indicated initial suppression of viral replication with a subsequent rise to levels higher than those in the untreated controls. In the brains of adenine arabinoside-treated animals, titers of virus gradually diminished to undetectable levels by the eighth day after institution of therapy. The purine nucleosides, cytosine arabinoside (ara-C) and its analogue adenine arabinoside (ara-A) are now being used in the treatment of systemic herpesvirus infections in humans [1-3]. The antiviral activity of these compounds has been demonstrated in vitro and in certain in vivo systems, but the main impetus for their current usage in man is their availability at a time when there is no proven specific therapy for these lifethreatening infections. Encephalitis due to herpes simplex virus (HSV) has been the focus of a number of attempts at treatment, mainly with ara-C [4-6], yet there is still no convincing proof that such treatment is effective. Part of the reason for this lack of proof is the extreme variability of the disease in man; this variability makes it difficult to assess drug efficacy when survival is the main criterion used for evaluation of therapy. Experimentation with animals has done little to clarify the issue, particularly concerning the relative effectiveness of these two compounds on survival and on elimination of virus from the
Evaluation of a Burkholderia Pseudomallei Outer Membrane Vesicle Vaccine in Nonhuman Primates

Burkholderia pseudomallei (Bps)is the causative agent of melioidosis and is endemic in regions of northern Australia and Southeast Asia. Bps is inherently resistant to multiple antibiotics and is considered a potential biological warfare agent by the U.S. DHHS. Therefore, effective vaccines are necessary to prevent natural infection and to safeguard against biological attack with this organism. In our previous work we have shown that immunization with naturally derived outer membrane vesicles (OMVs) from Bps provides significant protection against lethal aerosol and systemic infection in BALB/c mice. In this work, we evaluated the safety and immunogenicity of escalating doses of OMV vaccine in rhesus macaques. We show that immunization of rhesus macaques with Bps OMVs generates humoral immuneresponses to protective protein and polysaccharide antigens without any associated toxicity or reactogenicity. These results lay the groundwork for evaluation of protective efficacy of the OMV vaccine in the nonhuman primate model of melioidosis.
Effects of measurement techniques on the experimental characterization of crack tip opening angle-Δa resistance curves

One of the most promising approaches to characterizing the stable tearing process for lower constraint configurations in metallic materials has been indicated to be the crack tip opening angle (CTOA) criterion. In this paper we examine the effect of measurement distance selection and the impact of measurement procedures/analysis on the experimental CTOA-Δa resistance curve behavior of a Ti-6Al-4V and an Al5083 alloy. A new, systematic procedure for carrying out the experimental, surface CTOA measurement process has been used, which has uncovered artifacts of measurement distance selection that have not been presented prior to this study. By studying the CTOA-Δa behavior using a rigidly defined and consistent method, it is apparent that the measurement distance behind the crack tip at which angles are measured has a direct impact on the shape of the early transitional behavior of the CTOA-Δa behavior as well as the critical, experimental CTOA values produced.
Poor groups around strong gravitational lenses

Poor groups are common and interactive environments for galaxies, and thus are important laboratories for studying galaxy evolution. Unfortunately, little is known about groups at z ≥ 0.1, because of the difficulty in identifying them in the first place. Here we present results from our ongoing survey of the environments of strong gravitational lenses, in which we have so far discovered six distant ( z ≥ 0.5) groups of galaxies. As in the local Universe, the highest velocity dispersion groups contain a brightest member spatially coincident with the group centroid, whereas lower-dispersion groups tend to have an offset brightest group galaxy. This suggests that higher-dispersion groups are more dynamically relaxed than lower-dispersion groups and that at least some evolved groups exist by z ~ 0.5. We also compare the galaxy and hot gas kinematics with those of similarly distant clusters and of nearby groups.
Recombinant vascular endothelial growth factor 121 attenuates autoantibody-induced features of pre-eclampsia in pregnant mice

BACKGROUND Pre-eclampsia (PE) is a serious hypertensive disorder of pregnancy characterized by excessive production of a soluble form of the vascular endothelial growth factor (VEGF) receptor-1, termed soluble fms-like tyrosine kinase-1 (sFlt-1). This placental-derived factor is believed to be a key contributor to the clinical features of PE. Women with PE are also characterized by the presence of autoantibodies, termed angiotensin type 1 receptor activating autoantibody (AT1-AA), that activate the major angiotensin receptor, AT1. These autoantibodies cause clinical features of PE and elevated sFlt-1 when injected into pregnant mice. The research reported here used this autoantibody-injection model of PE to assess the therapeutic potential of recombinant VEGF121, a relatively stable form of the natural ligand.
Molecular chaperoning function of Ric-8 is to fold nascent heterotrimeric G protein α subunits

We have shown that resistance to inhibitors of cholinesterase 8 (Ric-8) proteins regulate an early step of heterotrimeric G protein α (Gα) subunit biosynthesis. Here, mammalian and plant cell-free translation systems were used to study Ric-8A action during Gα subunit translation and protein folding. Gα translation rates and overall produced protein amounts were equivalent in mock and Ric-8A–immunodepleted rabbit reticulocyte lysate (RRL). GDP-AlF4−–bound Gαi, Gαq, Gα13, and Gαs produced in mock-depleted RRL had characteristic resistance to limited trypsinolysis, showing that these G proteins were folded properly. Gαi, Gαq, and Gα13, but not Gαs produced from Ric-8A–depleted RRL were not protected from trypsinization and therefore not folded correctly. Addition of recombinant Ric-8A to the Ric-8A–depleted RRL enhanced GDP-AlF4−–bound Gα subunit trypsin protection. Dramatic results were obtained in wheat germ extract (WGE) that has no endogenous Ric-8 component. WGE-translated Gαq was gel filtered and found to be an aggregate. Ric-8A supplementation of WGE allowed production of Gαq that gel filtered as a ∼100 kDa Ric-8A:Gαq heterodimer. Addition of GTPγS to Ric-8A–supplemented WGE Gαq translation resulted in dissociation of the Ric-8A:Gαq heterodimer and production of functional Gαq-GTPγS monomer. Excess Gβγ supplementation of WGE did not support functional Gαq production. The molecular chaperoning function of Ric-8 is to participate in the folding of nascent G protein α subunits.
Sustained Donor Engraftment in Recipients of Double-Unit Cord Blood Transplantation Is Possible Despite Donor-Specific Human Leukoctye Antigen Antibodies

The impact of human leukocyte antigen (HLA) donor-specific antibodies (DSA) on cord blood (CB) engraftment is controversial. We evaluated the influence of pre-existing HLA-antibodies (HLA-Abs) on engraftment in 82 double-unit CB recipients (median age, 48 years) who underwent transplantation for hematologic malignancies. Of 28 patients (34%) with HLA-Abs, 12 had DSA (median mean fluorescence intensity 5255; range, 1057 to 9453). DSA patients had acute leukemia (n = 11) or myelodysplasia (n = 1) and all received either high-dose or reduced-intensity (but myeloablative) conditioning. After myeloablative CB transplantation (CBT) (n = 67), sustained donor engraftment was observed in 95% without HLA-Abs (median, 23 days), 100% with nonspecific HLA-Abs (median, 23 days), and 92% with DSA (median, 31 days, P = .48). Of 6 patients with HLA-Abs to 1 unit, 3 engrafted with that unit and 3 with the other. Of 6 patients with HLA-Abs against both units, 1 had graft failure despite being 100% donor, and 5 engrafted with 1 unit. Successful donor engraftment is possible in patients with DSA after myeloablative double-unit CBT. Our data suggest potential deleterious effects of DSA can be abrogated in patients with hematologic malignancies.
Red Flags: Cochlear Implant Programming

Consistent, full-time use of a well programmed cochlear implant (CI) is key for auditory and spoken language development. Young children with hearing loss often lack the requisite language skills t...