cssi/SciSciGPT-SciSciNet huggingface dataset:
Positional cloning of Sorcs1, a type 2 diabetes quantitative trait locus.

We previously mapped the type 2 diabetes mellitus-2 locus (T2dm2), which affects fasting insulin levels, to distal chromosome 19 in a leptin-deficient obese F2 intercross derived from C57BL/6 (B6) and BTBR T+ tf/J (BTBR) mice1. Introgression of a 7-Mb segment of the B6 chromosome 19 into the BTBR background (strain 1339A) replicated the reduced insulin linked to T2dm2. The 1339A mice have markedly impaired insulin secretion in vivo and disrupted islet morphology. We used subcongenic strains derived from 1339A to localize the T2dm2 quantitative trait locus (QTL) to a 242-kb segment comprising the promoter, first exon and most of the first intron of the Sorcs1 gene. This was the only gene in the 1339A strain for which we detected amino acid substitutions and expression level differences between mice carrying B6 and BTBR alleles of this insert, thereby identifying variation within the Sorcs1 gene as underlying the phenotype associated with the T2dm2 locus. SorCS1 binds platelet-derived growth factor, a growth factor crucial for pericyte recruitment to the microvasculature, and may thus have a role in expanding or maintaining the islet vasculature. Our identification of the Sorcs1 gene provides insight into the pathway underlying the pathophysiology of obesity-induced type 2 diabetes mellitus.
Prognostic factors in early breast carcinoma

Several investigators, the SEER data, and the ECOG/Intergroup study have shown that patients with small tumors ( or = 5 cm). Nuclear grade and tumor differentiation are established indicators; however, the interobserver lack of concordance has thwarted their use in clinical trials. The presence of peritumoral lymphatic and blood vessel invasion (PLBI) is associated with a relative risk of recurrence of 4.7. The predictive value of the presence of hormone receptors in tumors is associated with a favorable disease free and overall survival difference of 8-10%; however, this advantage is being eroded by the early appearance of other factors, such as the epidermal growth factor receptor (EGFR), proliferative capacity (S-phase), nuclear grade, and HER-2/neu oncogene. Concordance among the different methods of hormone-receptor assay (immunocytochemical, sucrose gradient, and dextran-coated charcoal) is essential to refine the true value of these factors. DNA flow cytometry measurements of ploidy (DNA content) and S-phase fraction are the most characterized of the prognostic factors. There are conflicting reports regarding the clinical significance of ploidy status, while measurements of S-phase fraction clearly indicate a robust association with disease free and overall survival. Our data continue to show that S-phase, but not ploidy, can predict time to recurrence significantly in untreated patients, even when data are stratified for tumor size. HER-2/neu oncogene is expressed in about 50% of ductal carcinoma in situ and 14% of invasive ductal carcinoma. The presence of this oncogene at high copy number may be a useful independent marker of poor prognosis and may be associated with drug resistance and correlated with tumor recurrence and shorter survival. EGFR could be measured in most breast tumors, and the level of its expression has inversely correlated with estrogen receptor protein expression. The value of EGFR as a predictor of prognosis remains controversial and is still being investigated. Cathepsin-D provides a provocative biologic rationale but is hindered by different and incongruent methods of analysis. The majority of large studies with more than 3-years' follow-up suggests that high cathepsin-D levels may be predictive of greater recurrence and lower survival. Angiogenesis has been implicated as a critical component of the metastatic process. Early studies show that tumor angiogenesis is an independent and highly significant prognostic indicator, and its presence may suggest the selection of "anti-angiogenic therapy."(ABSTRACT TRUNCATED AT 400 WORDS)
The frequency of bone marrow cells that bind erythropoietin.

The frequencies of rat and mouse bone marrow cells capable of binding erythropoietin were studied by both direct fluorescence and indirect immunofluorescence. We found that between 1–2% of the cells bound erythropoietin, that the binding was specific, and that the number of cells that bound erythropoietin was in part, a function of the erythropoietic state of the donor animal. A statistical method for evaluating the data obtained is included.
Closing the loop: p53-BCL6 feedback

Comment on Margalit et al, page [1599][1] Margalit and colleagues demonstrate that BCL6 expression is increased by p53, thus discovering a new feedback loop associating these 2 proteins—a finding that has numerous implications for our understanding of normal B-cell physiology and lymphoma
Lone Pair Functionality in Divalent Lead Compounds

The role of the lone pair of electrons of Pb(II) in determining the coordination geometry is analyzed from crystallographic studies and ab initio molecular orbital optimizations. Of particular interest are factors that contribute to the disposition of ligands around the lead with geometries that are (1) holodirected, in which the bonds to ligand atoms are distributed throughout the surface of an encompassing globe, and (2) hemidirected, in which the bonds to ligand atoms are directed throughout only part of an encompassing globe, i.e., there is an identifiable void in the distribution of bonds to the ligands. The preferred coordination numbers for lead were found to be 4 for Pb(IV) and 4 and 6 for Pb(II). All Pb(IV) structures in the CSD have a holodirected coordination geometry. Pb(II) compounds are hemidirected for low coordination numbers (2−5) and holodirected for high coordination numbers (9, 10), but for intermediate coordination numbers (6−8), examples of either type of stereochemistry are found. A...
Plasma levels of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and the risk of prostate cancer.

Abstract In the US, prostate cancer (PCa) has the highest incidence rate of all cancers in males, with few known modifiable risk factors. Some studies support an association between the Vitamin D metabolites, 1,25-dihydroxyvitamin D (1α,25(OH) 2 D 3 ) and/or 25-hydroxyvitamin D (25(OH)D 3 ), and prostate cancer, while others have yielded conflicting results. 1α,25(OH) 2 D 3 has anti-proliferative and pro-differentiating effects in prostate cancer cell lines, and levels of circulating 25(OH)D 3 may be important as PCa cells possess 1-α-hydroxylase activity. Using a nested case–control design, we evaluated whether plasma levels of 25(OH)D 3 and 1α,25(OH) 2 D 3 were associated with prostate cancer risk in participants from the Nutritional Prevention of Cancer (NPC) trial. With 83 cases and 166 matched controls, we calculated the adjusted odds ratios for increasing plasma levels of 25(OH)D 3 and 1α,25(OH) 2 D 3 . Compared to the lowest tertile of plasma 25(OH)D 3 levels, the adjusted odds ratios were 1.71 (0.68–4.34) and 0.75 (0.29–1.91); the corresponding odds ratios for 1α,25(OH) 2 D 3 were 1.44 (0.59–3.52) and 1.06 (0.42–2.66). Given the pivotal effects of the Vitamin D receptor on gene transcription, it is likely that the anti-carcinogenic effects of Vitamin D that have previously been described are related to the activity and expression of the Vitamin D receptor and should be investigated further.
Novel approach for low-voltage termination of anatomically defined reentry

Implantable cardioverter defibrillator (ICD) therapy for termination of cardiac arrhythmias is not optimal. High energy electrical shocks can cause side effects including electroporation, tissue damage, pain and traumatic patient experience. Reducing the shock energy would result in a profound improvement of the therapy. Eighty percent of patients receiving ICD therapy have a history of coronary artery disease and thus have the substrate for anatomically defined reentrant tachyarrhythmia. An applied electric field induces virtual electrode polarization at anatomical heterogeneities, which may also serve as the core of anatomical reentry. We have shown theoretically that interaction of the electric field with the core of reentry could potentially result in a 100-fold reduction of defibrillation energy. Methods and Results: We used a superfused isolated rabbit right ventricular preparation as a model of the endocardial border zone (n 14). Survival of only 50-200 m of the endocardial layer was verified by anti-Connexin43 immunostaining. Stable reentry was induced by burst pacing. Monophasic shocks (10 ms, 0.2-3.6 V/cm) were applied parallel to the endocardium from mesh electrodes located in the bath. Optical imaging revealed that the stable reentrant circuits were pinned to the endocardial trabeculae and were maintained with a cycle length of 155.78 38.58 ms. A total of 192 reentries were initiated and terminated by appropriately timed virtual electrode-induced excitation of either the anatomical obstacle serving as the core of reentry or a heterogeneity near the core. E50 (field at which 50% of reentries were terminated) was 1.4 V/cm, which corresponds to 3.4 times the average field excitation threshold. Conclusions: These results indicate that low-voltage termination of reentry is achievable and may be a promising new alternative to conventional ICD therapy.
Determination of Lead in Aqueous and Organic Media by Atomic-Absorption Spectroscopy

The sensitivities of lead in aqueous and organic media by atomic-absorption spectroscopy using lead lines 2170 A, 2833 A, and 4058 A, and an oxy-hydrogen or oxy-acetylene flame were studied. When lead in aqueous solution was complexed as K2PbI6 and the complex extracted into methyl isopropyl ketone, a threefold increase in sensitivity relative to the aqueous solution of lead (as lead nitrate) was obtained. Using a 178-mm-long adapter on the top of a Beckman integral aspirator-burner (oxy-hydrogen), a sensitivity (in ppm/1% absorption) of 0.007 and a standard deviation of 0.014 ppm were obtained with a sample containing 0.1 ppm lead. Results obtained with oxy-hydrogen and oxy-acetylene flames have been discussed, and the precision and detection limits indicated. A procedure to determine lead in ppb–ppm level by extracting lead as K2PbI6 in methyl isopropyl ketone has been prescribed.
Experimental Evidence for a Bragg Glass Density Wave Phase in a Transition-Metal Dichalcogenide

Analysis of the spatial dependence of current-voltage characteristics obtained from scanning tunneling microscopy experiments indicates that the charge density wave (CDW) occurring in ${\mathrm{NbSe}}_{2}$ is subject to locally strong pinning by a non-negligible density of defects, but that on the length scales accessible in this experiment the material is in a ``Bragg glass'' phase where dislocations and antidislocations occur in bound pairs and free dislocations are not observed. An analysis based on a Landau theory is presented showing how a strong local modulation may produce only a weak long range effect on the CDW phase.
Measuring familial sinistrality: problems with dichotomous classification.

Familial sinistrality (FS), or familial left-handedness, is usually measured as a presence/absence dichotomy (FS+/FS−). Measuring FS as a dichotomy is problematic in at least two ways: (1) magnitude data are discarded and (2) there is an increased risk of violating statistical assumptions. We hypothesised that using a non-dichotomised FS measure would allow more sensitive statistical tests than using a dichotomised measure. The non-dichotomised measure examined was proportion of family that is left-handed, or Proportional FS (FSP). FS measures of 60 healthy adults were consistent with our hypothesis: (1) The effect size was 2.3 times larger when FSP was used than when Dichotomised FS (FSD) was used; (2) the observed relationship was statistically significant when FSP was used but not when FSD was used; and (3) statistical assumptions were violated when FSD was used but not when FSP was used. When cases were weighted to account for an increased likelihood of FS in large families, results were similar. Next...
The Treatment of Poverty and Theodicy in the Syriac Translation of Ben Sira

This paper is aimed to address the relationship between the Hebrew and the Syriac versions of Ben Sira—and it will try to expose a coherent agenda on the part of the Syriac translator, explaining at least some of the differences between the two versions. The Syriac translator felt obliged to change the content of the original text's treatment of evil. He tended to stress human choice and mute Ben Sira's allusions to predestination and God's creation of Evil. Pointing out this tendency offers new perspectives on earlier scholarship, especially Winter (1977), who claimed that the Syriac version was biased against wealth.
Caput succedaneum mimicking a cephalocele

Caput succedaneum is relatively common at birth but infrequently diagnosed in utero. It has a benign prognosis, but it is very important not to misdiagnose it as a cephalocele, which carries a guarded prognosis. We present the case of a patient who experienced preterm labor and premature rupture of the membranes at 28 weeks' menstrual age. Our initial diagnosis was cephalocele, but after the male infant was delivered by cesarean section, examination revealed no bone defect, and our final diagnosis was caput succedaneum. We also discuss the sonographic findings and diagnostic differences between caput succedaneum, cephalocele, and other fetal head masses.
Killing two birds with one stone, maybe: CETP inhibition increases both high-density lipoprotein levels and insulin secretion

Connections between glucose and lipid metabolism have long been recognized. It is well known that impaired glucose metabolism, particularly in diabetes mellitus, influences plasma levels of both apoB- and apoAI-containing lipoproteins and induces an abnormal lipid phenotype known as atherogenic dyslipidemia.1 This is characterized by high triglycerides, low high-density lipoprotein (HDL), and elevated low-density lipoprotein (LDL) particle concentration attributable to a preponderance of smaller-sized LDL. These effects are seen as secondary to the insulin-resistant state and caused by its interference with the lipid homeostatic mechanisms, including increased secretion of apoB-containing lipoproteins and reduced lipolysis of triglyceride-rich particles. However, a direct influence of primary abnormalities in lipid metabolism on glucose homeostatic mechanisms is not commonly recognized, with the exception of subjects with extreme hypertriglyceridemia caused by lipoprotein lipase deficiency, where diabetes mellitus may develop during periods of uncontrolled dyslipidemia, and control of glucose levels is achieved by adjustment of triglycerides.2 Although lipotoxicity is known to harm many tissues and cells, the presence of common dyslipidemia is not considered as a risk factor for changes in insulin sensitivity by liver, muscle, or adipose tissue, or in insulin production by the pancreatic beta cell. Article, see p 167 In the past few years, this general concept has been challenged with the recognition that membrane cholesterol levels regulate insulin exocytosis from beta cells. In particular, the absence of the main cellular cholesterol transporter, ABCA1, drastically reduces insulin output.3,4 Because ABCA1 controls the first step in the extracellular process known as reverse cholesterol transport, mediated by the circulating HDL particle, this suggests that natural or drug-induced changes in HDL metabolism or composition may influence the ability of beta cells to respond to physiological stimuli, including glucose. Hence, it is possible that in some instances diabetes mellitus development may be accelerated …
Dehalogenation of Halogenated Fumigants by Polysulfide Salts

Halogenated fumigants are among the most heavily used pesticides in agriculture. Because of their high mobility and toxicological characteristics, the contamination of air or groundwater by these compounds has been a great environmental concern. In this study, we investigated dehalogenation of several halogenated fumigants by polysulfides. The reaction of polysulfides and methyl iodide (MeI), 1,3-dichloropropene (1,3-D), and chloropicrin (CP) was very rapid. When the initial fumigant and polysulfide concentrations were both 0.2 mM, the observed 50% disappearance time values (DT50) of MeI, cis-1,3-D, and trans-1,3-D were 27.2, 29.6, and 102 h, respectively. When the initial polysulfide concentration was 1.0 mM, the corresponding DT50values were only 2.2, 1.6, and 3.8 h. Under similar conditions, the reaction with CP was even more rapid than with the other fumigants. In 0.2 mM polysulfide solution, more than 90% of the spiked CP disappeared in 1 h after the initiation of the reaction. The reaction between f...
Targeting T cell responses by selective chemokine receptor expression.

Immune responses require the orchestrated migration of T cells throughout the body. Conventional CD4+ and CD8+ alphabeta T cells undergo clonal expansion in the secondary lymphoid tissues, during which they are programmed to migrate into specific non-lymphoid tissues and other lymphoid effector sites such as B cell follicles. By contrast, T cell populations expressing receptors with limited diversity (i.e. gammadelta T cells and NK T cells) appear to be preprogrammed to localize in non-lymphoid tissues where they monitor tissue integrity or serve regulatory functions. By promoting chemotaxis and integrin activation, chemokines and their receptors (in conjunction with surface adhesion molecules) control these T cell homing events. Thus, expression of chemokine receptors defines T cells with tropism for particular tissues and/or microenvironments, and identifies T cell subsets with distinct functional properties.
Preserve Your Privacy with PCO: A Privacy Sensitive Architecture for Context Obfuscation for Pervasive E-Community Based Applications

Context awareness is just beginning to revolutionize the ways we interact with networked devices. In order for context awareness to flourish, especially in a pervasive environment, users must be certain that their privacy is respected. Privacy in pervasive online community depends on the level of granularity of the provided information, user’s relation to possible recipients, and the possible usage of user’s data. Conventional privacy preservation techniques are not suitable for these pervasive applications. The notion of this paper is to present the preliminary results of using a unique architecture of obfuscation techniques to preserve users' privacy in e-community based applications. This paper describes our current work in developing a novel Privacy-sensitive architecture for Context Obfuscation (PCO) for privacy preservation in pervasive online community based applications. More specifically, PCO safeguards a user’s privacy by generalizing the contextual data (e.g. the user’s current activity) provided to the applications and distributed to the user’s peers. To support multiple levels of granularity for the released contextual data, the obfuscation procedure uses an ontological description that states the granularity of object type instances. We have developed and evaluated a contextual instant messaging application (PCO application) in Android platform that incorporates level-based privacy of the user’s contextual information. We also evaluate our prototype application through user evaluation survey.
Detection of Fibrous Strands on Prosthetic Mitral Valves With Transesophageal Echocardiography: Another Potential Embolic Source

Patients with prosthetic mitral valves (MVR) have an increased incidence of cardiac embolic events, but the causes of these emboli have not been determined. Fibrous strands, detected by transesophageal echocardiography (TEE) on the left atrial side of MVRs, may be embolic precursors in these patients. However, the incidence and clinical significance of these strands are unknown. We reviewed the charts of 76 consecutive patients with MVRs who underwent a total of 83 TEE studies between January 1991 and January 1992. Of the 83 studies, 39 (47%) were of bioprostheses and 44 (53%) were of mechanical prostheses. Strands were found in 15 studies (18%) and were significantly more common in mechanical prostheses (32% vs 3%; p p
Contracting and Franchising County Services in Florida

This study examines the privatization behavior of county governments and treats contracting and franchising as separate decision-making activities. Contracting decisions are influenced primarily by the desire to reduce production costs. Growth pressures and a political culture that favors professional administration over private-regarding politics also are determinants. Franchising decisions are influenced heavily by growth pressures, political impediments to altering the traditional public production arrangements, a political culture that insulates administration from politics, and a desire to keep tax rates down. In other words, franchising decisions are predicated extensively on efforts to limit the scope of government and operate county government according to businesslike principles.
Insulin-stimulated Phosphorylation of a Rab GTPase-activating Protein Regulates GLUT4 Translocation

Insulin stimulates the rapid translocation of intracellular glucose transporters of the GLUT4 isotype to the plasma membrane in fat and muscle cells. The connections between known insulin signaling pathways and the protein machinery of this membrane-trafficking process have not been fully defined. Recently, we identified a 160-kDa protein in adipocytes, designated AS160, that is phosphorylated by the insulin-activated kinase Akt. This protein contains a GTPase-activating domain (GAP) for Rabs, which are small G proteins required for membrane trafficking. In the present study we have identified six sites of in vivo phosphorylation on AS160. These sites lie in the motif characteristic of Akt phosphorylation, and insulin treatment increased phosphorylation at five of the sites. Expression of AS160 with two or more of these sites mutated to alanine markedly inhibited insulin-stimulated GLUT4 translocation in 3T3-L1 adipocytes. Moreover, this inhibition did not occur when the GAP function in the phosphorylation site mutant was inactivated by a point mutation. These findings strongly indicate that insulin-stimulated phosphorylation of AS160 is required for GLUT4 translocation and that this phosphorylation signals translocation through inactivation of the Rab GAP function.
Comparison of the Inhibitory Effects of Hydroxyurea, 5-Fluorodeoxyuridine, 3,4-Dihydroxybenzylamine, and Methotrexate on Human Squamous Cell Carcinoma

A cell line (SCC-25) derived form a human squamous cell carcinoma was found to have a higher level of in situ thymidylate synthase activity when compared to a faster-growing cell line, L1210 leukemia, and approximately 5 times the level of activity of a cell line with the same growth rate, S91-A melanoma. These results led to an examination of the effects of both direct and indirect inhibitors of this enzyme using intact SCC-25 cells. It was found that drugs that have an indirect effect on this enzyme–methotrexate (MTX), hydroxyurea (HU), and 3,4-dihydroxybenzylamine (3,4-DHBA)–acted as noncompetitive inhibitors and the inhibition of thymidylate synthase by these drugs did not result in the accumulation of its substrate, dUMP. This suggested that these drugs are also inhibiting steps leading to the formation of dUMP by a mechanism that is coordinated with the inhibition of thymidylate synthase f-Fluorodeoxyuridine (FUDR), a competitive inhibitor of thymidylate synthase, did cause an increase in the dUMP pool size indicating that this drug did not affect the synthesis of this substrate. There was a good correlation for the inhibition of growth, DNA synthesis, and thymidylate synthase with HU, 3,4-DHBA, and FUDR. However, the results suggested fundamentally different mechanistic reasons for the close relationship among these three inhibitory effects. Finally the inhibition of growth by MTX did not appear to correlate with the inhibition of DNA synthesis. The implication of these results for the therapy of epidermally derived proliferative disorders, especially with combinations such as MTX and 5-FU, is discussed.
Simplified meta-analysis of clinical trials in resuscitation.

Abstract Objective: To present and demonstrate a new simplified method for synthesizing results of multiple clinical trials in resuscitation research. Methods: The mean difference across studies in the proportion of favorable outcomes between experimental and control groups is calculated. This difference is shown to have a t -distribution. Its significance can be ascertained with a simple t -test. The analysis can be implemented in a one-page computer spreadsheet. Results: Simplified meta-analysis provides high sensitivity and can be extended to include weighting of studies according to size or quality, comparison of subgroups of studies, tests for outliers, and calculation of the power of the meta-analysis. Sample analyses are presented for two experimental forms of cardiopulmonary resuscitation (CPR): interposed abdominal compression (IAC) CPR and active compression–decompression (ACD) CPR. Conclusions: Traditional narrative reviews, taking note of the proportion of individual studies with statistically significant results, can lead to erroneous conclusions and unnecessary delays in the clinical use of research findings. Simplified meta-analysis can provide rapid, quantitative, and accurate estimates of the amount of benefit or harm from an experimental intervention and can further empower physicians to practice evidence-based medicine.
The Role of Alpha-Synuclein in Melanin Synthesis in Melanoma and Dopaminergic Neuronal Cells

The relatively high co-occurrence of Parkinson’s disease (PD) and melanoma has been established by a large number of epidemiological studies. However, a clear biological explanation for this finding is still lacking. Ultra-violet radiation (UVR)-induced skin melanin synthesis is a defense mechanism against UVR-induced damage relevant to the initiation of melanoma, whereas, increased neuromelanin (NM), the melanin synthesized in dopaminergic neurons, may enhance the susceptibility to oxidative stress-induced neuronal injury relevant to PD. SNCA is a PD-causing gene coding for alpha-Synuclein (α-Syn) that expresses not only in brain, but also in skin as well as in tumors, such as melanoma. The findings that α-Syn can interact with tyrosinase (TYR) and inhibit tyrosine hydroxylase (TH), both of which are enzymes involved in the biosynthesis of melanin and dopamine (DA), led us to propose that α-Syn may participate in the regulation of melanin synthesis. In this study, by applying ultraviolet B (UVB) light, a physiologically relevant stimulus of melanogenesis, we detected melanin synthesis in A375 and SK-MEL-28 melanoma cells and in SH-SY5Y and PC12 dopaminergic neuronal cells and determined effects of α-Syn on melanin synthesis. Our results showed that UVB light exposure increased melanin synthesis in all 4 cell lines. However, we found that α-Syn expression reduced UVB light-induced increase of melanin synthesis and that melanin content was lower when melanoma cells were expressed with α-Syn, indicating that α-Syn may have inhibitory effects on melanin synthesis in melanoma cells. Different from melanoma cells, the melanin content was higher in α-Syn-over-expressed dopaminergic neuronal SH-SY5Y and PC12 cells, cellular models of PD, than that in non-α-Syn-expressed control cells. We concluded that α-Syn could be one of the points responsible for the positive association between PD and melanoma via its differential roles in melanin synthesis in melanoma cells and in dopaminergic neuronal cells.
Comparison of the luminescence centers in a-As2Se3 and c-As2Se3 by time-resolved photoluminescence and photo-induced absorption measurements

Abstract The photoluminescence in the amorphous and crystalline forms of arsenic triselenide appears to arise from similar localized states. We have identified transient photo-induced absorption from the excited states of the luminescence centers in both forms. Measurements of the decay rates and absorption spectra of the luminescence centers in the crystal and the glass are compared. Differences between the crystal and the glass are discussed.
Modification of the clonogenic assay for the detection of lymphokine activated killer cell activity.

Abstract The soft agar clonogenic assay using [3H]thymidine uptake as an endpoint was adapted for the detection of human LAK activity against the Daudi lymphoma cell line and human tumor cells obtained by biopsy. Using Daudi cells as the target population the modified agar assay was more sensitive than the conventional 4 h 51Cr release assay. Use of a single layer agar assay allowed the assessment of LAK cytotoxic/cytostatic activity against Daudi lymphoma cells after cell to cell contact, while a two layer system permitted evaluation of the role of soluble mediators in LAK/target cell interactions. This study shows that LAK cells can either kill or inhibit the proliferation of Daudi cells by two mechanisms: one which requires cell-to-cell contact, and a second via soluble mediators. As determined by the use of neutralizing antisera, the soluble factor(s) are not tumor necrosis factor and interferon-γ. Of the nine individual human tumor samples obtained by biopsy, 89% were sensitive to allogeneic LAK cells when the two populations were admixed. Of these nine tumors 44% were inhibited by LAK-derived soluble factors. The soft agar assay system should serve as a useful tool for determining the sensitivity of human tumors to LAK cells and for studying the mechanisms of LAK anti-tumor activity.
Psychological distress mediates the effect of pain on function.

Abstract As part of a larger longitudinal study, the current analyses characterize the relationship among pain, psychological distress, and physical function after major lower extremity trauma. Structural equation modeling techniques were utilized to analyze data from a prospective 2-year observational study of 327 patients treated at 8 level I trauma centers. Data were gathered at 3, 6, 12, and 24 months after injury. In the models tested, higher levels of depressive and anxious distress at the preceding time point was related to lower levels of functioning at 6, 12, and 24 months, and higher levels of pain at the preceding time point were related to lower levels of functioning at 6 and 12 months, but not at 24 months. A reverse model in which lower levels of functioning led to higher levels of psychological distress or pain was tested and did not fit the data. The combination of depressive and anxious distress plays an increasingly important role in mediating the impact of pain on physical function as the recovery from lower extremity trauma progresses from early to later stages. Both pain and psychological distress contribute to reduced function during the first year after a serious injury; however, as recovery proceeds, the role of psychological distress in determining function increases.
Two‐dimensional 1H NMR studies of paramagnetic bimetallic mixed‐metal complexes

Synthetic dinuclear mixed-metal complexes have proved useful as models for metal-substituted dinuclear iron-oxo proteins. However, a detailed assignment of their paramagnetically shifted proton NMR resonances has thus far been difficult to achieve. In the light of the significant role of two-dimensional (2D) NMR techniques in establishing the bond connectivities in diamagnetic molecules, COSY studies were performed on a series of complexes, [Fe(II)M(II)BPMP(O2CCH2CH3)2]+ {BPMP = 2,6-bis [bis(2-pyridylmethyl)aminomethyl]-4-methylphenol, M Mn, Co and Zn}, taking advantage of the short electronic relaxation time of Fe(II). The resonances from the four distinct pyridine rings of each of the three complexes were unambiguously assigned based on the bond-correlated cross signals in the 2D spectra due to the (α-)β-γ-β′ pyridyl proton connectivities. The resonances from the two bridging ligands of these complexes were also unambiguously assigned based on the same approach. Together with longitudinal relaxation time (T1) measurements, the 2D data allow the assignment of all the paramagnetically shifted proton resonances of all the three bimetallic complexes.
Initial-state dependence of the quench dynamics in integrable quantum systems. II. Thermal states

We study properties of isolated integrable quantum systems after a sudden quench starting from thermal states. We show that, even if the system is initially in thermal equilibrium at finite temperature, the diagonal entropy after a quench remains a fraction of the entropy in the generalized ensembles introduced to describe integrable systems after relaxation. The latter is also, in general, different from the entropy in thermal equilibrium. Furthermore, we examine the difference in the distributions of conserved quantities in the thermal versus the generalized ensembles after a quench and show that they are also, in general, different from each other. This explains why these systems fail to thermalize. A finite-size scaling analysis is presented for each quantity, which allows us to make predictions for thermodynamically large lattice sizes.
Interpreting interrogatives as rhetorical questions

While an ordinary question seeks information or an answer from the hearer, a rhetorical question does not expect to elicit an answer. In general, a rhetorical question has the illocutionary force of an assertion of the opposite polarity from what is apparently asked. Under the rhetorical question reading, the yes—no questions Did I tell you that writing a dissertation was easy? and Didn't I tell you that writing a dissertation was easy? respectively assert I didn't tell you that writing a dissertation was easy and I told you that writing a dissertation was easy. I show that rhetorical questions and ordinary questions do not pattern alike with respect to various well-formedness conditions, such as negative polarity item licensing. I propose a way of deriving the interpretation of rhetorical questions and address why rhetorical questions have the interpretation of an assertion of the opposite polarity. I also argue that the representation over which various well-formedness conditions are stated is the output of a post-LF derivation which is determined via interaction with a sub-part of the interpretational component, namely pragmatics. I show that a compositional semantics for rhetorical questions is possible by directly mapping this post-LF representation onto the semantic interpretation. The approach pursued here has implications for the architecture of the grammar in general, and in particular for the nature of the interface between syntax and semantics/pragmatics.
A Nuclear Antagonistic Mechanism of Inhibitory Smads in Transforming Growth Factor-β Signaling

Inhibitory Smads (I-Smads), including Smad6 and Smad7, were initially characterized as cytoplasmic antagonists in the transforming growth factor-β signaling pathway. However, I-Smads are also localized in the nucleus. Previously, we have shown that Smad6 can function as a transcriptional co-repressor. In this study, we found both Smad6 and Smad7 interact with histone deacetylases (HDACs). Acetylation state of core histones plays a critical role in gene transcription regulation. An HDAC inhibitor, trichostatin A, released Smad6-mediated transcription repression. Moreover, class I HDACs (HDAC-1 and -3), not class II HDACs (HDAC-4, -5, and -6), were co-immunoprecipitated with Smad6. Endogenous HDAC-1 was also shown to interact with both Smad6 and Hoxc-8. Mapping of the interaction domain indicates Smad6 MH2 domain is mainly involved in recruiting HDAC-1. Most interestingly, Smad6 also binds to DNA through its MH1 domain, and the MH2 domain of Smad6 masks this binding activity, indicating that Smad6 MH1 and MH2 domains associate reciprocally and inhibit each other's function. Hoxc-8 induces Smad6 binding to DNA as a transcriptional complex. Our findings revealed that I-Smads act as antagonists in the nucleus by recruiting HDACs.
Towards improving the MITC9 shell element

Abstract Our objective in this paper is to present some results regarding the predictive capabilities of the MITC9 shell element when the tying points in the element are changed. The MITC9 element is a general nine-node shell element based on the formulation approach of using mixed-interpolated tensorial components. Different tying points are very simple to implement and are not decreasing the computational efficiency of the element. Hence, the use of the “best” tying points is clearly of value.
The effects of Minute loci and the possible involvement of transfer-RNA in sex chromosome non-disjunction in the Drosophila melanogaster male

This report shows that certain Minutes can greatly increase the frequency of sex chromosome non-disjunction in the In(1) sc4Lsc8R, 5Ey/y+Y system in the Drosophila melanogaster male. This effect is evaluated and discussed with special reference to the recent finding that the Minutes may be deficiencies of transfer RNA loci.
Immunity lessons and actions: Practical implications

SUMMARY Nutritional approaches can be used to improve disease resistance while mitigating the negative impact of immunity on bird performance. Supplying dietary nutrients at the appropriate times and amounts is critical for the development, maintenance, and function of the immune system. The immune system consists of multiple tissues and cell types, and when combined with the diversity of pathogens and routes of infection, the complexity of assigning nutrient requirements for immunity becomes apparent. Activation of the immune system reduces bird performance because of decreased food intake and changes in nutrient metabolism. Understanding the purpose of altered nutrient metabolism may help researchers develop nutritional strategies that complement, or support, the purpose of these catabolic responses to infection. Consequently, providing nutritional support to the immune system during times of critical need may help to mitigate the overall catabolic response to infection. To do so, the proper tools are needed for assessment and understanding of the desired responses from the immune system to particular pathogens. The immune system is dynamic and complex and requires proper care and feeding.
Treatment of Diaphragmatic Hernia Occurring After Transhiatal Esophagectomy.

Background Postesophagectomy diaphragmatic hernia (DH) is an uncommon problem but an important one to recognize and treat because of the risk of significant complications such as incarceration and strangulation. Diaphragmatic hernia appears to occur more frequently following transhiatal esophagectomy (THE) than after transthoracic procedures, likely because of the enlargement of the diaphragmatic hiatus required to perform THE.
Interactions of Calcium, pH, Temperature, and Chymosin During Milk Coagulation,

Abstract Holstein milk samples with good and poor chymosin-coagulation characteristics were coagulated in the Formagraph using different combinations of five levels of chymosin, three pH, and three temperatures in the presence and absence of .02% added calcium chloride. All the main factors significantly altered both coagulation time and curd firmness. Multiple comparisons of mean coagulation times showed that lower concentrations of chymosin (.01, .02, and .03 rennin units/ml milk) were significantly different in altering coagulation time and were different from higher concentrations (.04 and .05 rennin units/ml milk). The three pH produced significantly different mean coagulation times. Addition of more than .02 rennin units/ml milk was not necessary for adequate curd firmness in 30 min after chymosin addition where the pH of the milk was 6.4 or lower. Addition of .02% calcium chloride to milk was not necessary for adequate curd firmness 30 min after chymosin addition if other milk coagulation factors were adequately adjusted (pH ≤ 6.4; chymosin concentration = .02 rennin unit/ml milk; temperature = 37°C).
Increased levels of circulating intercellular adhesion molecule 1 in the sera of patients with rheumatoid arthritis

Objectdive. We sought to assess whether circulating levels of intercellular adhesion molecule 1 (ICAM-1) in patients with rheumatoid arthritis (RA) are elevated and correlate with clinical measures of disease activity and whether this ICAM-1 originates from the synovium. Methods. Circulating ICAM-1 (cICAM-1) levels were determined by sandwich enzyme-linked immunosorbent assay of serum from 61 RA, 18 osteoarthritis (OA), and 11 inflammatory arthritis (IA) patients. In addition, paired serum and synovial fluid samples were collected from 17 RA, 9 OA, and 4 IA patients. The stability of cICAM-1 was assessed by overnight incubation at 37°C. Finally, the potential degradative effects of synovial fluid proteases were assessed by incubation of recombinant soluble ICAM-1 with patient synovial fluid. Results. RA sera contained significantly greater (P < 0.001) levels of cICAM-1 compared with RA synovial fluid and compared with sera or synovial fluid from the OA and IA patients. Circulating ICAM-1 levels were unaffected by overnight incubation at 37°C and were unaffected by exposure to RA, OA, or IA synovial fluid. Serum levels of cICAM-1 demonstrated a weak, but significant (P < 0.05) correlation with the joint score and erythrocyte sedimentation rate in 25 RA patients treated with nonsteroidal antiinflammatory drugs. Conclusion. The greatest elevations of cICAM-1 were seen in RA patient sera. In both RA and OA, synovial fluid cICAM-1 levels were consistently lower than serum levels, suggesting that cICAM-1 did not originate in the synovium. Because the production of cICAM-1 can be increased by cytokines (e.g., interleukin-1, tumor necrosis factor α), elevated levels of circulating ICAM-1 in RA may be reflective of systemic exposure to elevated cytokine levels.
N-carboxymethylchitosan inhibition of aflatoxin production: Role of zinc

Aqueous Solutions of N-carboxymethylchitosan (NCMC) suppressed both growth and aflatoxin production byAspergillusflavus andA.parasiticus in submerged culture (Adye and Mateles A&M). Test media were amended with various concentrations of zinc (15, 30, 45, 60 uM), and NCMC solution (0.62 uM). After 8 days incubation NCMC-treated cultures showed marked reduction of aflatoxin production and fungal growth. Enhanced levels of zinc did not overcome the NCMC-mediated inhibition of fungal growth or aflatoxin production.
Unrestricted Hartree-Fock calculation of spin densities in some xanthyl radicals

Abstract Proton hyperfine coupling constants for some planar and non-planar xanthyl radicals are calculated by the unrestricted Hartree-Fock method and compared with the experimental data.
Uridine pharmacokinetics in cancer patients.

The availability of uridine can alter the sensitivity of tumor cells to antimetabolites such as N-phosphonacetyl-l-aspartic acid (PALA) and acivicin by virtue of the cell's ability to salvage preformed metabolites from its environment. We investigated the pharmacokinetics of physiologically relevant amounts of uridine in cancer patients in a pilot study to further our understanding of uridine metabolism in the human body. Four cancer patients, two males and two females, were given an i.v. bolus of a trace amount of radiolabeled uridine. The nucleoside disappeared from the plasma in a triphasic manner, with initial half-lives of 0.57±0.28 and 1.79±0.62 min and a terminal half-life of 17.5±7.3 min. The volume of distribution was 481±70 ml/kg, and the plasma uridine clearance was calculated to be 1.70±0.42 l/min. Simultaneous plasma and bone marrow uridine concentrations were measured in a separate group of seven healthy volunteers. The uridine concentration in plasma was 2.32±0.58 μM, and that in the bone marrow plasma was 10.44±5.06 μM. These results suggest a very rapid turnover of uridine in the plasma when the nucleoside is present at physiologic concentrations, and that there is a locally high concentration of uridine available for salvage in the bone marrow.
Micro-classifying diffuse large B-cell lymphomas.

MicroRNA profiles defined by signatures of normal B-cell subpopulations, genomic changes, and oncogene activity segregate diffuse large B-cell lymphomas into unique subgroups with potential clinical relevance.
Senescence-like growth arrest induced by hydrogen peroxide in human diploid fibroblast F65 cells

Human diploid fibroblast cells lose replicative potential after a certain number of population doublings. We use this experimental system to investigate the role of oxidative damage in cellular aging. Treating cells with H2O2 at < 300 microM did not affect the viability of the majority of cells when judged by morphology, trypan blue exclusion, and protein synthesis. However, the treatment caused a dose-dependent inhibition of DNA synthesis. After a 2-hr treatment with 200 microM H2O2, the cells failed to respond to a stimulus of serum, platelet-derived growth factor, basic fibroblast growth factor, or epidermal growth factor by synthesizing DNA, and the loss of response could not be recovered by 4 days. Subcultivation showed that, as in senescent cells, division of the treated cells was inhibited. The life-time cumulative growth curve showed that the loss of replication due to H2O2 treatment was cumulative and irreversible. The H2O2 treatment decreased the number of the population doublings in the rest of the life span by 35.3 +/- 10.3%. Enzymatic assays indicated that, like the cells in their senescent state, the treated cells were less able to activate ornithine decarboxylase and thymidine kinase. Furthermore, subcultivation after the H2O2 treatment showed that the cells developed the morphology of senescent cells. In conclusion, sublethal treatment of H2O2 "stunned" F65 cells and caused the cells to enter a state resembling senescence.
Dielectric capping effects on binary and ternary topological insulator surface states

Using a density functional based electronic structure method, we study the effect of crystalline dielectrics on the metallic surface states of Bismuth- and chalcogen-based binary and ternary three dimensional topological insulator (TI) thin films. Crystalline quartz (SiO2) and boron nitride (BN) dielectrics were considered. Crystalline approximation to the amorphous quartz allows to study the effect of oxygen coverage or environmental effects on the surface states degradation which has gained attention recently in the experimental community. We considered both symmetric and asymmetric dielectric cappings to the sufaces of TI thin films. Our studies suggest that BN and quartz cappings have negligible effects on the Dirac cone surface states of both binary and ternary TIs, except in the case of an oxygen-terminated quartz surface. Dangling bond states of oxygens in oxygen-terminated quartz dominate the region close to Fermi level, thereby distorting the TI Dirac cone feature and burying the Dirac point in the quartz valence band region. Passivating the oxygen-terminated surface with atomic hydrogen removes these dangling bond states from the Fermi surface region, and consequently the clear Dirac cone is recovered. Our results are consistent with recent experimental studies of TI surface degradation in the presence of oxygen coverage.
Juvenile Referrals in Texas: An Assessment of Criminogenic Needs and the Gap Between Needs and Services:

Researchers emphasize the importance of risk and criminogenic needs in developing intervention strategies for juvenile offenders. Yet, few jurisdictions collect information about the risk/needs profile of known youthful offenders or whether their needs are being addressed. This study estimated the prevalence of mental health, substance abuse, educational, and family-related needs for youths referred to seven juvenile probation departments in Texas, which represent 21% of referrals statewide. Analyses indicate that the most prevalent needs are problems associated with parental supervision, school behavior, school attendance, parental/family problems, disposition/self-image, and substance abuse. Additional analyses suggest that substantial gaps exist between the number of juveniles needing and receiving programs and services. It is concluded that such information is absolutely essential if policy makers are to formulate appropriate and adequate intervention strategies for court-involved youth.