cssi/SciSciGPT-SciSciNet huggingface dataset:
Progress on Ras/MAPK Signaling Research and Targeting in Blood and Solid Cancers

The mitogen-activated protein kinase (MAPK) pathway, consisting of the Ras-Raf-MEK-ERK signaling cascade, regulates genes that control cellular development, differentiation, proliferation, and apoptosis. Within the cascade, multiple isoforms of Ras and Raf each display differences in functionality, efficiency, and, critically, oncogenic potential. According to the NCI, over 30% of all human cancers are driven by Ras genes. This dysfunctional signaling is implicated in a wide variety of leukemias and solid tumors, both with and without viral etiology. Due to the strong evidence of Ras-Raf involvement in tumorigenesis, many have attempted to target the cascade to treat these malignancies. Decades of unsuccessful experimentation had deemed Ras undruggable, but recently, the approval of Sotorasib as the first ever KRas inhibitor represents a monumental breakthrough. This advancement is not without novel challenges. As a G12C mutant-specific drug, it also represents the issue of drug target specificity within Ras pathway; not only do many drugs only affect single mutational profiles, with few pan-inhibitor exceptions, tumor genetic heterogeneity may give rise to drug-resistant profiles. Furthermore, significant challenges in targeting downstream Raf, especially the BRaf isoform, lie in the paradoxical activation of wild-type BRaf by BRaf mutant inhibitors. This literature review will delineate the mechanisms of Ras signaling in the MAPK pathway and its possible oncogenic mutations, illustrate how specific mutations affect the pathogenesis of specific cancers, and compare available and in-development treatments targeting the Ras pathway.
Bible, Bees and Boxes

AbstractThis article tells the story of beekeeping in Palestine in the late Ottoman and early British rules. It focuses on a French-Swiss missionary family, the Baldenspergers, who introduced “modern beekeeping” to the area through the adoption of a new technology—the movable-frame beehive. Bees thus began to move to completely new places, produce different kinds of honey, and revolutionize the ecological and economic systems. The adoption of particular technological measures, by this manner, helped the family demonstrate that the land was literally “flowing with milk and honey.” As the governing rule increasingly encouraged this process, resistance came from other directions. In this regard, I examine theft as a way to resist to the creation of a holy land. I position the story of honey production in the larger context of European colonialism at the turn of the twentieth century, and the global search for “the ultimate race of bees.”
SU-E-J-122: The CBCT Dose Calculation Using a Patient Specific CBCT Number to Mass Density Conversion Curve Based On a Novel Image Registration and Organ Mapping Method in Head-And-Neck Radiation Therapy

Purpose: To develop a CBCT HU correction method using a patient specific HU to mass density conversion curve based on a novel image registration and organ mapping method for head-and-neck radiation therapy. Methods: There are three steps to generate a patient specific CBCT HU to mass density conversion curve. First, we developed a novel robust image registration method based on sparseness analysis to register the planning CT (PCT) and the CBCT. Second, a novel organ mapping method was developed to transfer the organs at risk (OAR) contours from the PCT to the CBCT and corresponding mean HU values of each OAR were measured in both the PCT and CBCT volumes. Third, a set of PCT and CBCT HU to mass density conversion curves were created based on the mean HU values of OARs and the corresponding mass density of the OAR in the PCT. Then, we compared our proposed conversion curve with the traditional Catphan phantom based CBCT HU to mass density calibration curve. Both curves were input into the treatment planning system (TPS) for dose calculation. Last, the PTV and OAR doses, DVH and dose distributions of CBCT plans are compared to the original treatment plan. Results: One head-and-neckmore » cases which contained a pair of PCT and CBCT was used. The dose differences between the PCT and CBCT plans using the proposed method are −1.33% for the mean PTV, 0.06% for PTV D95%, and −0.56% for the left neck. The dose differences between plans of PCT and CBCT corrected using the CATPhan based method are −4.39% for mean PTV, 4.07% for PTV D95%, and −2.01% for the left neck. Conclusion: The proposed CBCT HU correction method achieves better agreement with the original treatment plan compared to the traditional CATPhan based calibration method.« less
Are sexually permissive individuals more victimized and socially isolated

Sexually permissive individuals are judged harshly by others, yet little research has examined whether these individuals themselves feel more victimized and socially isolated. Among 810 undergraduates (74% females; 38% non-White; ages 18–23), linear, logistic, and negative binomial regressions indicated that, after controlling for demographics, higher numbers of lifetime casual sex partners predicted (a) more relational aggression experiences and sexual behavior-based prejudice, but (b) less loneliness, greater likelihood of having a best friend, and higher numbers of close friends, acquaintances, and relatives. Controlling for extraversion rendered most isolation, but not victimization, links nonsignificant. There were few sex differences. Results suggest a complex relation between permissiveness, victimization, and isolation, indicating resiliency among permissive individuals in the face of adversity.
7 Gametes and Fertilization in Flowering Plants

Publisher Summary This chapter discusses the plant gametes and fertilization, including current research and reviews on structure and function, and to compare the plant gametes and fertilization events with those in animals. Fertilization, a fusion of gametes, takes place, resulting in a zygote that grows into an embryo. In addition, a second fertilization between a sperm and the central cell also occurs, giving rise to endosperm, a nutritive tissue. Gametes in flowering plants are relatively sparse compared to gamete production, by marine invertebrates or by brown algae. Neither sperm nor eggs are readily released as in vertebrates or ferns. Flowering plant sperm resemble animal sperm, with condensed chromatin, reduced cell volume, and specialized cytoskeleton. The structure of plant eggs is unlike that of animal eggs; however, egg activation, by fertilization, is a similar phenomenon requiring sperm-egg fusion, migration of gamete nuclei in the egg, and nuclear fusion, followed by cell division. Research on fertilization, including blocks to polyspermy and egg activation, is at its inception. The tools for experimentation on fertilization are complex and not widely available. Simpler methods, with which to test in vitro fertilization, would be valuable.
Westward Impulse Embodied

A River Running West The Life of John Wesley Powell. Donald Worster. Oxford University Press, New York, 2000. 687 pp. $35. ISBN 0-19-509991-5. Worster9s biography of the explorer and scientist who became a patriarch of science-based government bureaus and the conservation of the American West places Powell and his fervor for reform in the context of the United States of his times.
Modeling the Effects of Area Closure and Tax Policies: A Spatial-Temporal Model of the Hawaii Longline Fishery

We develop an economic model for a multi-species fishery that incorporates the spatial and temporal distribution of effort and fish stocks. Catchability coefficients and initial stocks are estimated from catch and effort data for each specific location. Vessels are allocated over space and time to locations of maximum profit, which decline with harvest because of stock externalities. A supply function for labor allocation in the fishery is estimated. The simulated model is applied to the Hawaii longline fishery. The economic impacts of regulatory policies, such as reduction of inshore gear conflict and conservation of offshore turtle populations, are examined.
Nitric oxide inhibition in rats improves blood pressure and renal function during hypovolemic shock

We have examined the systemic and renal hemodynamic effects of nitric oxide (NO) inhibition with NG-monomethyl-L-arginine (L-NMMA) in normotensive rats as well as in rats with hypovolemic shock induced by hemorrhage. L-NMMA increased mean arterial blood pressure (MAP) from 114 +/- 4 to 130 +/- 6 mmHg (P less than 0.05) in the nonhemorrhaged rats and from 61 +/- 3 to 89 +/- 3 mmHg (P less than 0.05) in the hypovolemic animals. The absolute increase in MAP was greater in the hypovolemic (31 +/- 3 mmHg) than in the nonhemorrhaged (15 +/- 2 mmHg) rats (P less than 0.05). An excess of L-arginine reversed the increase in MAP induced by L-NMMA in both groups. In the normotensive rats the increase in blood pressure was associated with an elevation in renal vascular resistance (RVR; from 6.5 +/- 0.7 to 8.2 +/- 0.9 mmHg.ml-1.min-1, P less than 0.05) so that renal plasma flow (RPF) and glomerular filtration rate (GFR) were unchanged. In contrast, in the hypotensive rats, the marked increase in MAP induced by L-NMMA infusion was not associated with a significant increase in RVR. As a result L-NMMA increased both RPF (from 6.0 +/- 0.4 to 7.8 +/- 0.4 ml/min, P less than 0.05) as well as GFR (from 1.7 +/- 0.2 to 2.5 +/- 0.2 ml/min, P less than 0.05). We conclude that NO is produced and modulates peripheral resistance in normotensive rats as well as in rats with hypovolemic shock. In the hypovolemic rats NO inhibition substantially improves RPF and GFR.(ABSTRACT TRUNCATED AT 250 WORDS)
Enzyme/crystallins and extremely high pyridine nucleotide levels in the eye lens

Taxon-specific crystallins are proteins present in high abundance in the lens of phylogenetically restricted groups of animals. Recently it has been found that these proteins are actually enzymes which the lens has apparently adopted to serve as structural proteins. Most of these proteins have been shown to be identical to, or related to, oxidoreductases. In guinea pig lens, which contains zeta-crystallin, a protein with an NADPH-dependent oxidoreductase activity, the levels of both NADPH and NADP+ are extremely high and correlate with the concentration of zeta-crystallin. We report here nucleotide assays on lenses from vertebrates containing other enzyme/crystallins. In each case where the enzyme/crystallin is a pyridine nucleotide-binding protein the level of that particular nucleotide is extremely high in the lens. The presence of an enzyme/crystallin does not affect the lenticular concentrations of those nucleotides which are not specifically bound. The possibility that nucleotide binding may be a fac...
United States Food and Drug Administration Requirements for Approval of Generic Drug Products

As generic products become more available for the treatment of psychiatric disorders, clinicians must stay abreast of the U.S. Food and Drug Administration (FDA) requirements for the approval of generic drug products. The FDA declares that pharmaceutical equivalents only are therapeutically equivalent, and pharmacokinetic data are all that is usually required to determine therapeutic equivalence. The rationale behind the overall concept of bioequivalence is that if 2 pharmaceutical equivalents provide identical plasma concentration-time profiles in humans, there is no evidence to demonstrate that the 2 identical dosage forms will exhibit a difference in safety and efficacy. This article reviews current terminology used in abbreviated new drug applications for generic products, typical bioequivalence study designs, and FDA bioequivalence guidance for clozapine.
SIMPLE APPARATUS FOR THERMAL CONDUCTIVITY MEASUREMENTS OF UNCONSOLIDATED POWDERS

A transient technique for measuring the thermal conductivities of unconsolidated powders is described. The apparatus is fully automated and allows measurements to be made conveniently from room temperature to 800 K and in various void-fitting gases at pressures up to several atmospheres. Results are presented for the effective thermal conductivity of powdered iron carbide in several gases and the data are compared with the predictions of several simple models.
Historical perspectives on myelodysplastic syndromes

Although Georg Hegel quipped, "We learn from history that we do not learn from history", Aldous Huxley expressed a more nuanced view: "The charm of history and its enigmatic lesson consist in the fact that, from age to age, nothing changes and yet everything is completely different." In order to understand present-day positions and peculiarities in any field of human endeavor, familiarity with the past is essential. Those of us who study myelodysplastic syndromes (MDS) or care for patients diagnosed with these troublesome conditions may wonder also how the current state of affairs evolved with respect to our narrow area of focus, and how we know what we think we know now about these still-enigmatic bone marrow diseases. Here, I review a number of developments that collectively represent a brief "history of MDS." I first highlight a few landmark observations that preceded any concept of MDS by hundreds of years. Twentieth-century case descriptions and series with hypotheses about the etiology and nature of disorders described as "refractory anemia", "preleukemia", and with other terminology culminated in the efforts of the French-American-British (FAB) Co-operative Group of morphologists, whose landmark 1976 and 1982 papers provided the first widely-used classification of MDS. More recent developments in the MDS field include new mechanistic biological insights, regulatory approval of several somewhat-effective treatments, and improved organizational support and advocacy. The history of a disease concept like MDS, as for history in general, provides both inspiration and cautionary tales that can inform present and future work.
Feed-rate optimization with jerk constraints for generating minimum-time trajectories

Abstract Competitive pressure requires manufacturers to simultaneously address increasingly stringent constraints on both productivity and quality. From the perspective of numerically controlled (NC) machine tools, this means higher machining performance in terms of speed and accuracy. Conventional approaches to programming NC operations involve selecting a constant feedrate for a given operation to produce acceptable performance (operation time and contouring accuracy). In this paper, we examine the possibility of scheduling or varying the feedrate by taking into consideration the geometry of the contour that the machine is expected to follow and the physical capabilities of the machine (i.e., its maximum velocity, acceleration and jerk constraints). Previous work by the authors has addressed the efficient, off-line computation of time-optimal trajectories with constraints on velocity and acceleration. This paper introduces additional constraints on the permissible jerk (rate of change of acceleration) on the machine's axis. From a practical perspective, excessive jerk leads to excitation of vibrations in components in the machine assembly, accelerated wear in the transmission and bearing elements, noisy operations and large contouring errors at discontinuities (such as corners) in the machining path. The introduction of jerk into the feedrate scheduling problem makes generating computationally efficient solutions while simultaneously guaranteeing optimality a challenging problem. This paper approaches this problem as an extension of our previous bi-directional scan algorithm [23] , [29] . A new acceleration-continuation procedure is added to the feedrate optimization algorithm to address jerk constraints and remove discontinuities in the acceleration profile. The algorithm maintains computational efficiency and supports the incorporation of a variety of state-dependent (such as position, velocity, acceleration and jerk) constraints. By carefully organizing the local search and acceleration continuity enforcing steps, a globally optimal solution is achieved. Singularities, or critical points, and critical curves on the trajectory, which are difficult to deal within optimal control approaches, are treated in a natural way in this algorithm. Several application examples and tests are performed to verify the effectiveness of this approach for high-speed contouring.
Thermal deformation : From thermodynamics to heat transfer

An infinitesimal change in heat flux Q is shown, in terms of entropy flux Ψ = Q/T to have two parts, dQ =TdΨ + ΨdT, the first part being the thermal displacement and the sec-ond part being the thermal deformation. Only the second part dissipates into internal energy and generates entropy, This generation is shown to he dΠ =(Ψ/T)dT. Thermodynamic arguments are extended to transport phenomena
Chemotherapy combinations with monoclonal antibodies in non-Hodgkin's lymphoma.

Although the use of monoclonal antibodies as single agents has had a tremendous impact on the care of patients with non-Hodgkin’s lymphoma (NHL), the greatest benefit has been generated by the addition of monoclonal antibodies to conventional cytotoxic chemotherapy. Rituximab is the monoclonal antibody responsible for all clinical improvement noted to date. The addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy (R-CHOP regimen) improves the response rate, progression-free survival (PFS), and overall survival (OS) in diffuse large B-cell lymphoma (DLBCL). Adding rituximab to CHOP chemotherapy improves response rates and PFS in mantle cell lymphoma (MCL). Finally, the addition of rituximab to a variety of chemotherapy regimens improves the response rates, PFS, and OS in follicular lymphoma (FL). Several other (epratuzumab, bevacizumab, alemtuzumab) monoclonal antibody–chemotherapy combinations are currently under study in NHL. This review will summarize the data supporting the addition of rituximab to chemotherapy in NHL and discuss preliminary data regarding the use of other monoclonal antibodies in combination with chemotherapy.
Intraspecific Chromosome Number Variation and Prairie Restoration—A Case Study in Northeast Iowa, U.S.A

Genome duplication has played an important role in plant evolution. Variation in genome size within species is common, particularly in grasses, but rarely considered when planning restorations. We surveyed ploidy variation within one habitat (tall grass prairie) in one region (northeast Iowa, U.S.A.) to assess the risk of ploidy mismatch in restoration plantings. Genome sizes were estimated using flow cytometry for samples from 19 remnant prairies, 5 restoration plantings, and 2 seed sources. Intraspecific ploidy variation in remnant prairie populations was found for two species of grasses, Andropogon gerardii (big bluestem) and Panicum virgatum (switchgrass). Restoration seeds differed from remnants in ploidy for three species of grass, P. virgatum, Sorghastrum nutans (Indian grass), and Spartina pectinata (prairie cordgrass), and for one species of forb, Amorpha canescens (lead plant). In the case of S. pectinata, local ecotype seeds were found to consist of two different ploidy levels. Restorations in grasslands in the United States and elsewhere are likely to create mixed ploidy populations, probably resulting in lower reproductive success for the remnant population. Prevention of mixed ploidy populations will require the screening of restoration seed sources and regional surveys for ploidy variation.
Conceptual Tempo and Memory-Encoding Processes for Aurally Presented Words.

Summary The purpose of this study was to investigate, through the analysis of word recognition errors, the relationship between conceptual tempo and developmental changes in the bases for memory organization (phonetic or semantic). Following one presentation of a 69-item study list 96 reflective and impulsive third- and sixth-grade boys and girls were presented a recognition test list which contained words that were semantically or phonetically related to words which had appeared in the study list. Neither conceptual tempo nor age was clearly related to the number or type of recognition errors made. It is suggested that the previously demonstrated superiority of reflective, relative to impulsive, feature-analytic processes may be restricted to conditions of visual presentation.
Aerosol Penetration Behavior of Respirator Valves

Exhalation and inhalation valves from half-facepiece negative pressure respirators were evaluated for leakage during an 8-hour cyclic breathing test period using two work rates (415 and 622 kg-m/min) and two particle sizes (0.3 and 0.8 µm). Three different models (manufacturers) of exhalation valves were tested, with two lots for each model. Exhalation valve leakage ranged from 0.0 to 0.03%; no failure of exhalation valves occurred. No differences in lot or manufacturer were found. Differences in particle size did not lead to differences in penetration at the lower work rate; at the higher work rate 0.3-µm particles were less penetrating than 0.8-µm particles (0.03 versus 0.06%). When tested for air leakage at a pressure of 2.54 cm H2O, following the National Institute for Occupational Safety and Health certification method, exhalation valves exhibited no leakage either before or after the experiments. Inhalation valves averaged 20% leakage for all experiments; 0.3-µm particles were again less penetrating...
Experimental lead encephalopathy in the suckling rat: Concentration of lead in cellular fractions enriched in brain capillaries

Five-day old rats subjected to short-term (2-day) lead exposure by gastric gavage of aqueous lead acetate at the highest non-lethal dosage (1mgPb/g body weight/day) developed a hemorrhagic encephalopathy. Capillaries and microvessels isolated from brains of these rats showed abnormal morphology consisting of an increased number of irregularly dispersed endothelial nuclei and swollen, vacuolated endothelial cells. Lead was concentrated in isolated brain capillary-microvessel fractions, as demonstrated by both atomic absorption and 210Pb tracer methods. When lead exposure was continued for 20 days (at the maximal dosage regime compatible with a 60% survival rate), the rats recovered from the initial encephalopathy and capillaries and microvessels isolated from brains of these rats appeared morphologically normal. This recovery occurred despite continued high levels of lead in the blood and in the isolated capillary-microvessel fractions, suggesting that, as capillary endothelial cells mature, they are able to adapt to the presence of large amounts of lead.
Antioxidants attenuate endotoxin-induced activation of alveolar macrophages.

Background. Endotoxin (lipopolysaccharide [LPS]) stimulation of tissue-fixed macrophages induces the generation of toxic oxidants. However, recent studies also implicate redox changes in both the signal transduction pathways for cytokine genes and the generation of physiologically active arachidonic acid metabolites. Because cytokines and arachidonic acid metabolites initiate and perpetuate deleterious systemic inflammatory reponses, we tested whether macrophage activation could be modulated by antioxidants. Methods. Rabbit alveolar macrophages were obtained by bronchoalveolar lavage, isolated, treated with the antioxidants vitamin E or N-acetylcysteine (NAC), and stimulated with an optimal dose of LPS (10 ng/ml). Assays were performed for tumor necrosis factor (TNF), procoagulant activity, and prostaglandin E2. Total cellular RNA was extracted for Northern blot analysis of TNF messenger RNA. Results. Exposure of the macrophage to the antioxidants vitamin E and NAC inhibited TNF production, accumulation of TNF messenger RNA, procoagulant activity expression, and prostaglandin E2 production. Conclusions. Macrophage signal transduction of LPS is dependent on the generation of reactive oxygen intermediates that can be blocked both at the level of the lipid membrane (vitamin E) and at the intracellular level (NAC). This suggests a potential therapeutic role for antioxidants in disease states such as adult respiratory distress syndrome and multiple organ failure syndrome, which are characterized by excessive macrophage activation.
Efficient Monte Carlo simulation of rarefied flow in a small nozzle

The flow of carbon dioxide through a small conical nozzle is computed using two different numerical approaches. The first of these is the direct simulation Monte Carlo method in which the physical phenomena are modeled at the molecular level. The second technique solves the Navier-Stokes equations of fluid flow. The purpose of the paper is to compare the solutions generated by these two methods for the conditions prevailing in a small, low density nozzle. The comparison between the two sets of solutions reveals only small differences. However, the flow properties in the thick viscous layer close to the nozzle at the exit plane show important deviations which have implications for the subsequent determination of the plume backflow.
#116-S prevalence and correlates of cesarean section in an indian health service population

Abstract PURPOSE: To determine prevalence and correlates of cesarean section in a Native American population. METHODS: Obstetrical logbook records were abstracted for all (n = 798) Native American women delivering liveborn infants at an Indian Health Service hospital in New Mexico during the period 1/1/1996 through 12/31/1999. Univariate and multivariate analyses were conducted to examine demographic, prenatal, obstetric, intrapartum, and fetal factors in relation to type of delivery (cesarean vs. vaginal). Twin births and elective repeat cesareans were excluded from these latter analyses. RESULTS: The cesarean section rate for Native American women in the present study (9.7%; 95% confidence interval (CI): 7.7, 12.0) was far below rates for the state of New Mexico (16.7%) and national data (21.2%) for the same time period. Nulliparity, specific medical diagnoses during pregnancy, use of pitocin, length of labor >12.1 hours, arrested labor, fetal distress, presence of meconium, and malpresentation were each associated with cesarean deliveries in unadjusted analyses. There was a significant interaction between arrested labor and use of pitocin (p = 0.032). Among women with arrested labor, use of pitocin (odds ratio [OR] = 7.4) and presence of meconium (OR = 4.9) remained in the final logistic model. Among women with no arrested labor, a history of hypertension or diabetes during pregnancy (OR = 3.2), nulliparity (OR = 2.4), and a physician (vs. midwife) labor attendant (OR = 3.1) were independent correlates of cesarean section in multivariate analyses. CONCLUSION: In contrast to studies in other populations, cesarean deliveries among Native American women in this Indian Health Service hospital appeared to occur primarily based on medical need, not socioeconomic or demographic factors.
Pancreatic Cancer in Hereditary Pancreatitis: Consensus Guidelines for Prevention, Screening and Treatment

Pancreatic cancer is the fourth largest cancer killer among adults in the USA [1] and one of the top ten cancer killers in Europe and industrialized countries [2, 3]. Eighty-five to 90% of patients present with disease that is not resectable at the time of diagnosis [4]. Of those who undergo ‘curative’ resection, 5-year survival ranges from 10 to 24%, depending on the study quoted [4]. Against this dismal background, three strategies have emerged in the fight against this deadly disease: (1) prevention through risk factor reduction and vaccine development; (2) screening of high-risk groups in an attempt to identify tumors at a curable stage, and (3) improved neoadjuvant, surgical, adjuvant and palliative therapy. Hereditary pancreatitis (HP) is an autosomal dominant disorder with an estimated 80% phenotypic penetrance typically consisting of recurrent episodes of acute pancreatitis, frequent progression to chronic pancreatitis and an approximately 50to 70-fold increased risk of pancreatic cancer [5, 6]. Well over 200 kindreds have been identified worldwide. The criteria for diagnosis of HP are thoroughly discussed within another consensus document in this issue [7]. Mutations in the cationic trypsinogen gene (R122H, N29I) cause the disease in 60–70% of kindreds [8–12]. In vitro biochemical studies suggest that these mutations enhance trypsin activity within vesicular compartments of pancreatic acinar cells [13–16]. Additional mutations in the same gene have been identified (A16V, D22G, K23R) [17–21]. Unfortunately, inadequate clinical data and small numbers have so far precluded establishment of a cause-and-effect relationship for these mutations [22, 23]. The autosomal dominant inheritance pattern and high phenotypic penetrance of HP, our ability to confirm the diagnosis through genetic testing in up to 70% of kindreds and the high tumor risk make it an ideal model for prevention and screening protocols. The growing awareness of HP and the responsible gene defects mandates that we as pancreatologists provide guidelines with regard to cancer prevention, screening and therapy in these patients. It was with this intent that pancreatologists, scientists, surgeons, pathologists and geneticists convened at the Third International Symposium on Inherited Diseases of the Pancreas in Milan, Italy from April 5 to 7, 2001 (see www.inherited-diseases-pancreas.com). The following sections of this paper summarize the consensus recommendations, supported by the Council of the International Association of Pancreatology and others. These recommendations apply only to patients with HP and should not be applied to patients with other risk factors for pancreatic cancer or sporadic tumors [24, 25].
Self-reported false confessions and false guilty pleas among offenders with mental illness

Persons with mental illness may be at risk for false admissions to police and to prosecutors because of the defining characteristics of mental illness, but potentially because of heightened recidivism rates and increased opportunities. We surveyed 1,249 offenders with mental disorders from six sites about false confessions (FCs) and false guilty pleas (FGPs). Self-reports of FC ranged from 9 to 28%, and FGPs ranged from 27 to 41% depending upon site. False admissions to murder and rape were rarely reported. We also examined differences between those claiming false admissions and those not. Minorities, offenders with lengthier criminal careers, and those who were more symptomatic were more likely to have self-reported false admissions than their counterparts.
Stress‐strain behavior of the craze

The constitution and properties of crazes in glassy polymers and their relation to crack propagation are reviewed. New evidence is discussed which shows the craze to be much softer than the parent polymer but capable of sustaining large stresses and strains up to the point of failure. Craze failure is much more dependent on polymer molecular weight than is craze formation, and this difference is reflected in changes in both fracture surface morphology and crack toughness with molecular weight. Finally craze mechanical properties are thought to be integrally related to the mechanical behavior of high impact plastics.
Neurotransmitters involved in mediating the steroid-dependent suppression of pulsatile luteinizing hormone secretion in anestrous ewes: effects of receptor antagonists.

Seasonal anestrus in the ewe results from two effects of inhibitory photoperiods: a steroid-dependent effect by which estradiol gains the capacity to suppress LH pulse frequency and a steroid-independent effect that decreases LH pulse frequency in ovariectomized ewes. We have previously proposed that these effects of anestrous photoperiods result from the activation of inhibitory neuronal mechanisms at this time of year. In the present study, we used specific receptor antagonists to test this hypothesis and identify the neurotransmitters involved. Initially, eight receptor antagonists were screened for their ability to increase pulsatile LH secretion in ovary-intact anestrous ewes. Of these, only pimozide, a dopaminergic antagonist, and phenoxybenzamine, an a-adrenergic antagonist, increased LH pulse frequency. In contrast, neither pimozide nor phenoxybenzamine increased pulsatile LH secretion in midluteal phase ewes during the breeding season. These drugs did, however, produce other biological responses ...
The Presence of Arginine Regulates the Selectivity and Binding Affinity of Lysine Receptors

Post-translational modifications play an essential role in biological processes, such as gene expression and disease development. The methylation of lysine (Lys) on a histone protein, for example, can cause a gene to be repressed or activated. Dynamic combinatorial chemistry has been used to identify A2N as a synthetic receptor for trimethyllysine (Kme3). Recent studies have shown that A2N binds to Kme3 tighter than to non-methylated lysine (Kme0). When a neighboring arginine (Arg) was mutated to glycine, the binding of A2N to Kme0 and Kme3 weakened and A2N became more selective for Kme3. In sequences containing three Arg, A2N proved to bind to Kme0 and Kme3 significantly tighter as compared to the previous sequences. However, in this case A2N was considerably less selective for Kme3. We hypothesized that the presence of Arg affects the binding affinity and selectivity of Lys and by shifting the position of Arg further from Lys the binding would greatly weaken. We noticed that when Arg was shifted further from Kme0 and Kme3 the binding of A2N weakened, only partially in the tri-methylated state. As the distance between Arg and Lys increased A2N became more selective for Kme3. These findings suggest that Arg mediates the specificity of the binding affinity between Lys and A2N independent of location within the sequence with an improved selectivity for Kme3 as distance between Lys and Arg increased. The attraction between Arg and Lys will need to be further examined to understand the mechanism influencing the selectivity and binding properties of A2N to Lys. Increasing awareness of this relationship may help to modify synthetic receptors and better understand post-translational modifications.
A Power-Scalable Channel-Adaptive Wireless Receiver Based on Built-In Orthogonally Tunable LNA

Most of the traditional RF circuits are static or minimally tunable using some digital controllability. For example, high power, low power and shut down modes are available in some commercially available transceivers. If available, the tuning knobs affect different specifications in an interdependent manner, resulting in changing several specifications when only one needs to be tuned. This is not enough for power optimal operation of complete self-aware self-adaptive circuits and systems. Independent or orthogonal tunability of the important conflicting specifications using built-in tuning knobs allow optimal adaptation of the wire-less systems. In this paper we demonstrate the design and benefits of orthogonal tuning knobs using an inductorless LNA as a test vehicle. The design of an orthogonally tunable LNA is discussed that has a 14 dB Gain tuning range and 30 dB OIP3 tuning range as its power consumption goes down by 20×. Measurement results on this LNA validate the concept of orthogonal tunability. Use of this orthogonally tunable LNA within an adaptive wireless receiver framework shows power savings of 2× compared to a static system and an extra savings of 22% compared to a traditional nonorthogonal adaptive system.
When unexpected behavior is attributed to the environment

Abstract Two experiments were conducted to investigate a modification of the Jones and Davis (1965) analysis of attribution. Subjects were confronted with a situation in which there were two possible causes for an event, and differential information about these causes was provided such that subjects were much more informed about the nature of one potential cause than the other. This information also imparted to the subjects a definite expectancy about the forthcoming event. When the event disconfirmed subjects' expectancies, responsibility was attributed to the cause about which least was known. This result was found in both experiments. In addition, Experiment II offered some suggestive evidence that a disconfirmed expectancy will lead the person to direct his attention toward potential causes about which he is uninformed.
Optimal scheduling of cyclic batch processes for heat integration. I: Basic formulation

Abstract Significant savings in the utility cost of batch plants can be obtained by heat integration coupled with the rescheduling of operation times. In this work, efficient scheduling models are developed for maximization of heat recovery for the case of no intermediate storage with holding time (NIS) in cyclically operated single-product campaigns. In this development, the product recipe network is assumed to take the form of an arborescence and each unit is assumed to be assigned to a single task. A mixed integer linear programming (MILP) formulation is proposed to determine the operating schedule for maximum heat integration between the batch streams to reduce the utility consumption. Solution of this formulation can be readily obtained with a commercial MILP solver. Numerical examples are presented to illustrate the scope of the problems which can be handled with the formulation.
Geometric structure and surface vibrations of Cu(001) determined by medium-energy ion scattering.

We have investigated the geometric structure and the vibrational properties of Cu(001) with medium-energy ion scattering. The surface structure follows the common trend for metal surfaces. The surface relaxation is found to be small and oscillatory with a top-layer contraction (\ensuremath{\Delta}${\mathit{d}}_{12}$) of -2.4% and a second-layer expansion (\ensuremath{\Delta}${\mathit{d}}_{23}$) of +1%. In addition, we find that the surface vibrational amplitude is enhanced (as is usually the case) by \ensuremath{\sim}80%. A detailed analysis of our data shows an unexpected anisotropy of the vibrational amplitude, such that the out-of-plane vibrational amplitude is 30% smaller than the in-plane vibrational amplitude. This anisotropy can be removed by adsorbing 1/4 monolayer of sulfur on the surface. Our results are discussed in the context of surface stress and surface contractions.
Television advertising and profitability

Abstract To date, economists have largely ignored the possibility that various advertising media may have differential impacts on firm performance. Here an empirical analysis reveals that television advertising has a significantly greater positive impact on firm profitability than does advertising in general.
Plasma corticosteroid and chloride dynamics in rainbow trout, Atlantic salmon, and lake trout during and after stress

Levels of plasma corticosteroids and chloride were studied in rainbow trout (Salmo gairdneri), lake trout (Salvelinus namaycush), and Atlantic salmon (Salmo salar) after 6 h of confinement in a shallow dipnet. Plasma corticosteroids increased more sharply in rainbow trout than in the other species during the confinement, and returned to resting levels more slowly. Plasma chloride levels decreased significantly from resting levels in both rainbow trout and Atlantic salmon confined for 6 h and had not recovered 12 h after release from the dipnet; very little effect was observed in lake trout. Both plasma corticosteroid and chloride dynamics appear to vary widely in closely related species. The differences do not appear to be related to ease of maintaining the species in captivity.
Homogeneous multicomponent azeotropic batch distillation

Mixed waste-solvent streams generated in pharmaceutical and specialty chemical manufacturing typically form multicomponent azeotropic mixtures. This highly nonideal behavior often prevents separation and recovery of the solvents. Batch distillation remains an important separation technology for these industries. The sequence of pure component and azeotropic cuts produced in batch distillation depends strongly on the feed composition. For ternary- and four-component mixtures the separation behavior can be studied graphically in residue-curve maps. For mixtures with more components, this approach is infeasible. Other tools are therefore required. Deficiencies in earlier work on ternary systems are demonstrated and addressed as well as a complete set of concepts to describe batch distillation of an azeotropic mixture with an arbitrary number of components. The body of theory is derived from the fields of nonlinear dynamics and topology.
Treatment of recurrent malignant glioma by repeated intracerebral injections of human recombinant interleukin-2 alone or in combination with systemic interferon-alpha. Results of a phase I clinical trial.

Nine patients with a recurrent malignant glioma were treated with repeated intracavitary or intracerebroventricular injections of human recombinant interleukin-2 (rIL-2) alone or in combination with systemic interferon-α (IFN-α). Five patients received only rIL-2 and four were treated with rIL-2 plus subcutaneous injections of IFN-α. Therapy was administered on a Monday, Wednesday, Friday schedule for up to 10 weeks, beginning with a dose of 10,000 IU rIL-2/injection. Doses were escalated every two weeks until some toxicity was apparent. The maximum amount of rIL-2 any one patient in this group received was 580,000 IU. Patients on combination immunotherapy were held at an rIL-2 dosage of 10,000 IU while IFN-α, which began at 3 million IU, was escalated every other week up to 18 million IU/dose. They were then held at that IFN-α dosage and rIL-2 was increased to 50,000 IU. The total amount of rIL-2 and IFN-α any one in this group received was 510,000IU and 417 million IU, respectively. Repeated injections of 10,000 IU rIL-2 were well-tolerated by all nine patients and no change in their functional status was seen. At doses at 50,000 IU. rIL-2, increased edema around the tumor cavity was observed by MRI/CT scand in 3/5 patients and clinical side-effects in the form of somnolence and headache along with some morbidity specifically associated with tumor location were also seen. Patients receiving rIL-2 + IFN-α showed progressive fatigue, muscle weakness, and occasionally nausea. Two of these patients showed increased peritumoral edema on MRI/CT scan. Neither hematological abnormalities nor changes from baseline values were seen in blood samples from any of the patients. MRI/CT scans made at the conclusion of immunotherapy indicated tumor progression in two of the patients treated with rIL-2 alone while no tumor growth at the site of treatment occurred in the other two or in the four treated with the combination of rIL-2 and IFN-α. Further clinical testing of rIL-2 in combination with IFN-α is indicated.
Algorithms for Genome-Scale Phylogenetics Using Gene Tree Parsimony

The use of genomic data sets for phylogenetics is complicated by the fact that evolutionary processes such as gene duplication and loss, or incomplete lineage sorting (deep coalescence) cause incongruence among gene trees. One well-known approach that deals with this complication is gene tree parsimony, which, given a collection of gene trees, seeks a species tree that requires the smallest number of evolutionary events to explain the incongruence of the gene trees. However, a lack of efficient algorithms has limited the use of this approach. Here, we present efficient algorithms for SPR and TBR-based local search heuristics for gene tree parsimony under the 1) duplication, 2) loss, 3) duplication-loss, and 4) deep coalescence reconciliation costs. These novel algorithms improve upon the time complexities of previous algorithms for these problems by a factor of n, where n is the number of species in the collection of gene trees. Our algorithms provide a substantial improvement in runtime and scalability compared to previous implementations and enable large-scale gene tree parsimony analyses using any of the four reconciliation costs. Our algorithms have been implemented in the software packages DupTree and iGTP, and have already been used to perform several compelling phylogenetic studies.
pH-Controlled Oxidation of an Aromatic Ketone: Structural Elucidation of the Products of Two Green Chemical Reactions

A laboratory experiment emphasizing the structural elucidation of organic compounds has been developed as a discovery exercise. The “unknown” compounds are the products of the pH-controlled oxidation of 4′-methoxyacetophenone with bleach. The chemoselectivity of this reaction is highly dependent on the pH of the reaction media: under basic conditions, the haloform reaction cleaves the methyl ketone yielding 4-methoxybenzoic acid, but under acidic conditions, electrophilic aromatic substitution of the aromatic ring occurs to generate 3′-chloro-4′-methoxyacetophenone. Each product was characterized by physical methods including melting point determination, IR and proton and carbon NMR spectroscopies, and mass spectrometry. Students analyzed the experimental data to determine the structures of the products. The experiment allows for an introduction of the concepts of chemoselectivity and regioselectivity and a discussion of redox reactions in organic chemistry. In addition, since the reactions were conducted...
MATERNAL LIFESTYLES STUDY (MLS): EFFECTS OF SUBSTANCE EXPOSURE DURING PREGNANCY ON ACUTE MATERNAL OUTCOMES. † 1527

Reports of maternal/infant toxicity due to drug exposure during pregnancy are inconsistent. A large, collaborative, prospective, observational study(MLS) was initiated to better define exposure effects. Between May, 1993 and May, 1995, of 19,079 maternal/infant dyads screened for cocaine/opiate (C/O) exposure at four clinical centers (Brown U, U of Miami, U of Tenn, Memphis and Wayne State U), 16,982 (85%) met eligibility criteria and 11,810 (62%) agreed to participate. Exposure (EXP) was defined as an admission of C/O use or the presence of C/O metabolites in meconium using a central GC/MS assay. Of the consenting mothers, 50% were black, 60% were single, and 61% were Medicaid recipients. In this high risk cohort, 93% had at least one prenatal care visit(median-10 visits). Significant (p < 0.01) differences between EXP(n = 1185)and /non-C/O exposed(NON) (n = 10,625) mothers included:Table
Surface Modification of Tungsten Oxide-Based Photoanodes for Solar-Powered Hydrogen Production

We report on the development of tungsten-oxide-based photoelectrochemical (PEC) water-splitting electrodes using surface modification techniques. The effect of molybdenum incorporation into the WO3 bulk or the surface region of the film is discussed. Our data indicate that Mo incorporation in the entire film (WO3:Mo) results in poor PEC performances, most likely due to defects that trap photo-generated charge carriers. However, compared to a pure WO3 (WO3:Mo)-based PEC electrode, a 20% (100%) increase of the photocurrent density at 1.6 V vs. SCE is observed if the Mo incorporation is limited to the near-surface region of the WO3 film. The resulting WO3:Mo/WO3 bilayer structure is formed by epitaxial growth of the WO3:Mo top layer on the WO3 bottom layer, which allows an optimization of the electronic structure induced by Mo incorporation while maintaining good crystallographic properties.
Clinical use of cytokines in the treatment of myelodysplastic syndrome (MDS): A review

Myelodysplastic syndrome (MDS) is a frustrating disorder which until recently lacked effective treatment. Patients usually succumb to infection, bleeding complications, and/or progression to acute leukemia. Recombinant cytokines, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte (G) CSF, interleukin (IL) 3 and erythropoietin (Epo), have now been used to ameliorate the cytopenias associated with this disease. Small clinical trials in MDS patients using cytokines with myeloid activity (G-CSF, GM-CSF, IL-3) have shown consistent elevations in the WBC counts with little success in elevating hemoglobin or platelets. Epo is able to increase the hemoglobin in a small group of MDS patients. Future trials utilizing combinations of these cytokines may lead to multilineage effects.