cssi/SciSciGPT-SciSciNet huggingface dataset:
Geochemical evolution of a karst stream in Devils Icebox Cave, Missouri, USA

Abstract A 3.7 km flowpath along the main stream channel in Devils Icebox Cave, Boone County, Missouri, was sampled on 23 January, 23 March and 18 September 1994. In January 1994, the water was oversaturated with respect to both calcite and dolomite, and only minor compositional changes were observed along the flowpath. In March 1994, the water was oversaturated with respect to calcite but undersaturated with respect to dolomite. Using a mass-balance approach, the composition of the stream water at downstream locations was predicted by dissolution of dolomite (a maximum of 0.16 mmol s −1 ) and by a minor amount of calcite precipitation (a maximum of 0.03 mmol s −1 ). In September 1994, there were increases in the Mg, Ca, and total inorganic carbon (TIC) mass fluxes that were due to the dissolution of dolomite ( SI dolomite SI is saturation index) and calcite ( SI calcite 2 of the water should decrease downstream; however, we found an increase in the partial pressure of CO 2 along the stream. The source of this additional CO 2 is thought to be microbial degradation of bat guano. The decomposition of bat guano appeared to change the composition of the stream water during the period the bats are in the cave, and this change was reflected in the composition of the stream water collected in September 1994. Based on the length of the flowpath and on the average velocity of the water along the flowpath, the travel time of water in this karst stream is less than 4 days. The reactions that control the chemistry of the karst water must be those with equally short characteristic times: the dissolution of dolomite and calcite, CO 2 exchange, and microbial degradation of organic matter.
Hepatitis C Virus Protease Gene Diversity in Patients Coinfected with Human Immunodeficiency Virus

The clonal variability of the hepatitis C virus (HCV) protease gene in 24 individuals with HCV genotypes 1a, 1b, 2b, and 3a who were coinfected with the human immunodeficiency virus was evaluated. Within-genotype variability at the nucleotide and amino acid levels ranged from 6.5 to 8.6% and 2.2 to 3.8%, respectively. After adjustments were made for correlation of intrapatient clonal variation, mixed-model analysis indicated that nucleotide and amino acid variability among patients with different genotypes did not differ significantly. However, within individual patients, clonal variability differed by up to 5.3% and 5.8% at the nucleotide and amino acid levels, respectively, and genotype 1a had significantly greater nucleotide variability than other genotypes (P = 0.01). Significant variability exists within HCV protease gene variants at the patient level and could affect the effectiveness of HCV protease inhibitors.
Itinerant antiferromagnetism in the nearly-heavy-fermion compound NpSn 3

${\mathrm{NpSn}}_{3}$, with a paramagnetic electronic specific-heat coefficient \ensuremath{\gamma}, of 242 mJ/mol ${\mathrm{K}}^{2}$, undergoes an antiferromagnetic phase transition at 9.5 K with a resultant drop in \ensuremath{\gamma} to 88 mJ/mol ${\mathrm{K}}^{2}$. This behavior of \ensuremath{\gamma} (reduction by 64%) is typical of the ``heavier'' fermion antiferromagnets ${\mathrm{U}}_{2}$${\mathrm{Zn}}_{17}$, ${\mathrm{UCd}}_{11}$, and ${\mathrm{CePb}}_{3}$. Self-consistent linear-augmented-plane-wave calculations within the local-density approximation have been performed for both phases to study this effect. The calculations include both spin-orbit and magnetic coupling on the same level throughout the self-consistency process. An electronic specific-heat coefficient of 102 mJ/mol ${\mathrm{K}}^{2}$ is found for the paramagnetic phase---the largest value ever reported from a band-structure calculation. This large value implies that large enhancements observed in other heavy-fermion materials are not present in ${\mathrm{NpSn}}_{3}$. A specific-heat coefficient of 39.7 mJ/mol ${\mathrm{K}}^{2}$ was found for the antiferromagnetic phase, yielding a calculated 61% reduction in \ensuremath{\gamma} as a consequence of undergoing the phase transition. A total moment of 0.21${\ensuremath{\mu}}_{B}$ was obtained (-0.18 spin, 0.39 orbital) indicating the itinerant nature of the magnetism. An analysis of the dramatic reduction in electronic specific heat through the transition, as well as the temperature dependence of C/T in the paramagnetic phase, is presented along with a discussion of the implications for the other heavy-fermion antiferromagnets.
Standoff terahertz wave generation from two-color laser-induced plasma at 30 meters in ambient air

Terahertz wave generation and detection using gaseous medium as both the THz wave emitter and sensor has drawn a great deal of attention. We report intense THz wave generation from two-color laser-induced air plasma at standoff distances of up to 30 m with peak THz electric field exceeding 1 kV/cm.
Happiness, Rationality, Autonomy and the Good Life

The paper starts with a general discussion of the concepts of happiness and the good life. I argue that there is a conceptual core of happiness which has to do with one’s life as a whole. I discuss affective and attitude or life satisfaction views of happiness and indicate problems faced by those views. I introduce my own view, the life plan view, which sees happiness as the ongoing realizing of global desires of the person. I argue that on such a view one’s life could be happy without a high level of rationality or a high level of autonomy; such rationality and autonomy are not built into the concept of happiness. So while happiness is a final value, and good for the person, it is not the only final value. Rationality and autonomy are also final values and, where they exist, are good as ends for the person, part of the good life.
Response features across the auditory midbrain reveal an organization consistent with a dual lemniscal pathway

The central auditory system has traditionally been divided into lemniscal and nonlemniscal pathways leading from the midbrain through the thalamus to the cortex. This view has served as an organizing principle for studying, modeling, and understanding the encoding of sound within the brain. However, there is evidence that the lemniscal pathway could be further divided into at least two subpathways, each potentially coding for sound in different ways. We investigated whether such an interpretation is supported by the spatial distribution of response features in the central nucleus of the inferior colliculus (ICC), the part of the auditory midbrain assigned to the lemniscal pathway. We recorded responses to pure tone stimuli in the ICC of ketamine-xylazine-anesthetized guinea pigs and used three-dimensional brain reconstruction techniques to map the location of the recording sites. Compared with neurons in caudal-and-medial regions within an isofrequency lamina of the ICC, neurons in rostral-and-lateral regions responded with shorter first-spike latencies with less spiking jitter, shorter durations of spiking responses, a higher proportion of spikes occurring near the onset of the stimulus, lower thresholds, and larger local field potentials with shorter latencies. Further analysis revealed two distinct clusters of response features located in either the caudal-and-medial or the rostral-and-lateral parts of the isofrequency laminae of the ICC. Thus we report substantial differences in coding properties in two regions of the ICC that are consistent with the hypothesis that the lemniscal pathway is made up of at least two distinct subpathways from the midbrain up to the cortex.
How Are the Mighty Fallen: Rejected Classic Articles by Leading Economists

The authors asked the world's leading economists to describe instances in which journals rejected their articles. More than sixty essays, by a broadly diverse group that includes fifteen Nobel Prize winners, indicate that most have suffered publication rejection, often frequently. Indeed, journals have rejected many papers that later became classics. The authors discuss the prize-winners' experiences, other notable cases, and rejections by John Maynard Keynes when he edited the Economic Journal. Finally, they search in economists' almost universal experience of rejection for patterns and lessons about the publication process.
Body weight set point studies in weanling rats with dorsomedial hypothalamic lesions (DMNL rats)

Abstract In order to further characterize a previously postulated “organismic” set point, weanling DMNL and control (CON) rats were maintained on lab chow ad lib (AL) for 55 post-operative days. Subsequently, some DMNL and CON rats were food-restricted (REST) to 80% of the food intake of their AL-fed counterparts for 24 days. At this point, representative rats from each group were killed by decapitation and the remaining animals were re-fed AL and killed 7 and 22 days thereafter. At the end of REST, both DMNL and CON showed significant weight loss, which was greater in CON than in DMNL rats. After 7 days of refeeding, DMNL rats normalized their body weights but re-fed CON still weighed less than AL-fed CON 22 days after refeeding. Food intake in formerly REST groups overshot on refeeding for 7 days, but this was significant only in DMNL rats. Notably, during this time formerly REST-DMNL ate as much as AL-fed CON. Efficiency of food utilization was normal in DMNL during AL feeding and became reduced on REST as it did in REST-CON. Notably, on refeeding formerly REST-DMNL rats overshot that of AL-fed DMNL rats by the same magnitude as previously REST-CON overshot the values of AL-fed CON. After 22 days of refeeding, this overshoot was still evident in DMNL but not in CON. At the end of the REST period, plasma insulin and glucose were similar in AL-fed DMNL and AL-fed CON. They were significantly and comparably reduced in both REST-DMNL and REST-CON compared to the AL-fed DMNL and AL-fed CON. On refeeding these changes normalized within seven days. At the end of REST, plasma free fatty acid concentrations were higher in REST-DMNL and RESTCON than in AL-fed DMNL and AL-fed CON. After seven days of refeeding they normalized only in formerly RESTCON. Plasma glycerol and total protein were normal throughout all groups, as was carcass protein. Carcass fat was equivalently reduced in both DMNL and CON at the end of REST and normalized 7 days after refeeding. AL-DMNL had the same carcass fat as AL-CON and REST-DMNL had the same carcass fat as REST-CON. In conjunction with previously reported normal anabolic hormone levels the data suggest that DMNL rats are not growth-retarded but are merely scaled down in size without compromise of their homeostatic competence. We take this as strong evidence for the existence of an “organismic” set point.
In vivo Time-Resolved Brain Phosphorus Nuclear Magnetic Resonance

Methods used to obtain and quantify high-quality time-resolved dog brain phosphorus nuclear magnetic resonance (31P NMR) spectra are described. In eight animals the normoxic dog brain spectra showed 10% of total phosphorus in ATP, 14% in phosphocreatine (PCr), and 38% in brain phospholipids containing phosphodiesters. The chemical shift between PCr and inorganic phosphate, 5.09, corresponded to an intracellular brain pH of 7.2. During hypoxia, PCr declined to 0.5 ± 0.3 (n = 8) of starting levels, prior to any changes in brain ATP. Simultaneous recording of the EEG was obtained in two animals. During hypoxia, progressive PCr depletion was associated with progressive slowing of the EEG, which was essentially silent before significant changes occurred in brain ATP. Finally, the brain 31P NMR spectrum and pH were measured at 90-s intervals, and the sequential changes that followed respiratory arrest were monitored in one dog until high-energy phosphate depletion was complete.
Synthesis of the N2-deoxyguanosine adduct of the potent dietary mutagen IQ.

After bioactivation, the potent dietary mutagen 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ) reacts with DNA to give two regioisomeric adducts of deoxyguanosine. The synthesis of the minor N2-adduct has been achieved utilizing the Buchwald−Hartwig palladium-catalyzed N-arylation reaction as the key step.
Volcanic activity at Tvashtar Catena, Io

Abstract Galileo's Solid State Imager (SSI) observed Tvashtar Catena four times between November 1999 and October 2001, providing a unique look at a distinctive high latitude volcanic complex on Io. The first observation (orbit I25, November 1999) resolved, for the first time, an active extraterrestrial fissure eruption; the brightness temperature was at least 1300 K. The second observation (orbit I27, February 2000) showed a large ( ∼ 500 km 2 ) region with many, small, hot, regions of active lava. The third observation was taken in conjunction with Cassini imaging in December 2000 and showed a Pele-like, annular plume deposit. The Cassini images revealed an ∼ 400 km high Pele-type plume above Tvashtar Catena. The final Galileo SSI observation of Tvashtar (orbit I32, October 2001), revealed that obvious (to SSI) activity had ceased, although data from Galileo's Near Infrared Mapping Spectrometer (NIMS) indicated that there was still significant thermal emission from the Tvashtar region. In this paper, we primarily analyze the style of eruption during orbit I27 (February 2000). Comparison with a lava flow cooling model indicates that the behavior of the Tvashtar eruption during I27 does not match that of simple advancing lava flows. Instead, it may be an active lava lake or a complex set of lava flows with episodic, overlapping eruptions. The highest reliable color temperature is ∼ 1300 K . Although higher temperatures cannot be ruled out, they do not need to be invoked to fit the observed data. The total power output from the active lavas in February 2000 was at least 10 11 W .
Time-Dependent Sensitization of Heart Rate and Blood Pressure over Multiple Laboratory Sessions in Elderly Individuals with Chemical Odor Intolerance

Abstract In this study, we tested the hypothesis that low-level chemical odor intolerance (i.e., “cacosmia”) is a manifestation of heightened sensitizability to environmental stimuli. We examined supine heart rate and blood pressure of elderly individuals, who were classified as either having a higher degree of chemical odor intolerance (n = 12) or a lower degree of chemical odor intolerance (n = 13), upon awakening in a sleep research laboratory on 6 different days during an 8-wk protocol. During the 2 initial wk, they consumed a customary baseline diet (including ad lib milk and other dairy products), followed by 3 wk each of nondairy-containing and dairy-containing diets in randomly assigned, counterbalanced order. Measurements were made on 3 pairs of successive days, distributed over a 6-wk period, and on which different diets were consumed. The high-intolerance group had significantly higher mean supine systolic and diastolic blood pressures than did the low-intolerance group. Although subjects consu...
The Annual Cycle of Small Mammal Populations on a Zambian Floodplain

Several species of rodents and shrews live on the Kafue River Flats when they are not covered by floodwaters. Mastomys natalensis is usually the most abundant. Pelomys fallax, Crocidura mariquensis , and C. occidentalis often are common in wet sites. Breeding begins late in the dry season and is at its height during the rains. Populations are built up at this time, and as floodwaters rise over a period of several months they are forced to the margins of the floodplain, where they sometimes form dense refugee populations. As the flood slowly recedes they follow it out, and by the end of the dry season the few surviving animals are confined largely to marshy areas near the river. Body weight and fat deposits decrease during the dry season. Live-trapping studies suggest that populations are unstable throughout the year, with few animals resident in an area for more than a few weeks. Small mammals adapt to the unstable environment of the Flats by moving about more than populations in more stable environments and by breeding rapidly when conditions permit
Efficacy and toxicity of a CD22-targeted antibody-saporin conjugate in a xenograft model of non-Hodgkin's lymphoma.

Antibody drug conjugates (ADCs) can deliver potent drugs to cancer cells by employing the specificity of monoclonal antibodies (mAbs). ADCs have demonstrated significant anticancer activity and, in 2011, brentuximab vedotin has been approved by the FDA for the treatment of Hodgkin's and anaplastic large cell lymphomas. CD22 is an ideal target for ADC against B-cell malignancies because of its lineage-specific expression and rapid internalization upon antibody binding. In this study, we evaluated the anti-CD22 mAb HB22.7 as a vehicle for the targeted delivery of the potent toxin saporin (SAP). In vitro, HB22.7-SAP was cytotoxic against a panel of non-Hodgkin's lymphoma (NHL) cell lines representing the most common types of the disease. Moreover, in a xenograft model of NHL, HB22.7-SAP significantly inhibited the growth of established lesions and completely prevented tumor development when treatment was initiated within 24 h from tumor-cell inoculation. HB22.7-SAP had no significant in vivo toxicity. In conclusion, HB22.7 constitutes a potential platform for CD22-targeted ADCs.
Equine retained placenta: Technique for and tolerance to umbilical artery injections of collagenase

Under laboratory conditions and in clinical experiments, bacterial collagenase has proven to be effective in hydrolyzing placenta and detaching cotyledon from caruncle in the bovine species. Laboratory studies in which placental samples were incubated with collagenase have also demonstrated that collagenase is 3.7 times more effective in hydrolyzing equine placenta than bovine placenta. This led to the hypothesis that collagenase may be a potential treatment for mares with retained placenta. However, that collagenase may hydrolyze the uterine wall and perforate the uterus was a concern. It was the purpose of this study thus to determine any adverse effects of collagenase on the equine uterus and to develop a method for intraplacental injection of collagenase. Three normally expelled intact placentas from Arabian mares, 10 cyclic mixed-breed mares, and 4 mares of various breeds with retained placenta were used. Fluoroscein dye and latex were used to study the placental vasculature and to determine a suitable dose of collagenase; placentas were hydrolyzed by collagenase solution in vitro. Bacterial collagenase solution (40,000 units, 200 ml) was infused into the uterine lumen of each cyclic mare. Uterine biopsies were obtained from the mares before collagenase infusion and again at 16 h and 26 d after infusion. In the mares with retained placenta, each placenta was infused via its umbilical cord vessels with 200,000 units of bacterial collagenase in 1 L of saline. Results showed that none of the uteri from cyclic mares were damaged by collagenase treatment. During a 4-wk period of monitoring (including endoscopy) mares with retained placenta did not show any abnormalities. Retained placentas were expelled in less than 6 h after collagenase treatment. It was concluded that intraplacental injections of collagenase are a safe and potentially effective treatment for retained placenta in mares.
A mathematical tumor model with immune resistance and drug therapy: an optimal control approach

We present a competition model of cancer tumor growth that includes both the immune system response and drug therapy. This is a four-population model that includes tumor cells, host cells, immune cells, and drug interaction. We analyze the stability of the drug-free equilibria with respect to the immune response in order to look for target basins of attraction. One of our goals was to simulate qualitatively the asynchronous tumor-drug interaction known as “Jeffs phenomenon.” The model we develop is successful in generating this asynchronous response behavior. Our other goal was to identify treatment protocols that could improve standard pulsed chemotherapy regimens. Using optimal control theory with constraints and numerical simulations, we obtain new therapy protocols that we then compare with traditional pulsed periodic treatment. The optimal control generated therapies produce larger oscillations in the tumor population over time. However, by the end of the treatment period, total tumor size is smaller than that achieved through traditional pulsed therapy, and the normal cell population suffers nearly no oscillations.
Internet 3.0: Ten Problems with Current Internet Architecture and Solutions for the Next Generation

The basic ideas of the Internet architecture were developed 30+ years ago. In these 30 years, we have learnt a lot about networking and packet switching. Is this the way we would design the Internet if we were to start it now? This paper is an attempt to answer this question raised by US National Science Foundation, which has embarked on the design of the next generation Internet called GENI. In this paper, we point out key problems with the current Internet Architecture and propose directions for the solutions. We propose a general architectural framework for the next generation Internet, which we call Internet 3.0. The next generation Internet should be secure. It should allow business to set their boundaries and enforce their policies inside their boundaries. It should allow governments to set rules that protect their citizens on the Internet the same way they protect them on other means of transports. It should allow receivers to set policies for how and where they receive their information. They should have freedom to select their names, IDs and addresses with as little centralized control as possible. The architecture should be general enough to allow different governments to have different rules. Information transport architecture should provide at least as much control and freedom as the goods transport networks provide. We propose the framework of an architecture that supports all these requirements.
Critical illness is associated with decreased plasma levels of coenzyme Q10: A cross-sectional study

Abstract Purpose Plasma coenzyme Q10 (CoQ10) levels are lower in patients with septic shock (SS) than in healthy controls (HCs). However, CoQ10 status in critically ill patients without SS is unknown. Here, we investigated CoQ10 concentrations in patients with SS and without SS as compared with HCs. Materials and Methods We enrolled 36 critically ill patients and 18 HCs. Plasma CoQ10 concentrations were measured, and patients' clinical and demographical data were collected. Results Plasma CoQ10 concentrations were lower in critically ill patients (0.50 ± 0.36 μg/mL, P Conclusions Decreased plasma CoQ10 levels are not specific to patients with SS, but rather observed in a broad range of critically ill patients. In critically ill patients, CoQ10 insufficiency may be associated with various conditions; age may be a risk factor.
A systematic review of rates and diagnostic validity of comorbid adult attention-deficit/hyperactivity disorder and bipolar disorder.

Objective: Adult attention-deficit/hyperactivity disorder (ADHD) is increasingly recognized and reported to frequently coexist with bipolar disorder. Concurrent diagnosis of adult ADHD and bipolar disorder remains controversial. In this study, we conducted a systematic review to examine the rates and diagnostic validity of the concept of comorbid adult ADHD and bipolar disorder. Data Sources: MEDLINE, Embase, PsycInfo, and Cochrane databases were searched for articles published before March 30, 2007, using the keywords manic, bipolar, attention deficit hyperactivity, and adult. The computer search was supplemented with bibliographic cross-referencing. Study Selection: Exclusion criteria were studies with only pediatric subjects, childhood ADHD only but not adult ADHD, and either bipolar disorder or ADHD only, but not both; review articles, case reports; letters to the editor; and book chapters. Of the 262 citations found, 12 studies met our inclusion criteria. Data Extraction: Specific diagnostic validating criteria examined were phenomenology, course of illness, heredity, biological markers, and treatment response. There were 6 studies on comorbid rates, 4 on phenomenology, 3 on course of illness, 2 on heredity, none on biological markers, and 1 on treatment response. Data Synthesis: The proposed comorbid syndrome is fairly common (present in up to 47% of adult ADHD and 21% of bipolar disorder populations), with a more severe course of illness compared with that of bipolar disorder alone, and high rates of comorbidity with other psychiatric disorders. Its treatment appears to require initial mood stabilization. Conclusions: Comorbid adult ADHD and bipolar disorder has been insufficiently studied, with more emphasis on comorbidity rates and few data on course, neurobiology, heredity, and treatment. The diagnostic validity of adult ADHD/ bipolar disorder as a true comorbidity is not well-established on the basis of this equivocal and insufficient literature. More studies are greatly needed to further clarify its diagnostic validity and treatment approach.
Locating anomalies by gravity gradiometry using the matched filter with a probabilistic assessment

The matched filter can be used to identify the location of a specific signal embedded in background correlated noise. The maximum filter output indicates the likely location and, with appropriate statistical assumptions on the noise, it also serves as a test statistic in the probabilistic evaluation of the filter’s performance. Different setups of the Neyman-Pearson statistical hypothesis test yield predictions of either the probability of a miss or that of a false alarm. The needed statistics of the maximum filter output are properly obtained using the distribution of order statistics. Through Monte Carlo simulations, we analyzed the ability of the matched filter to identify a sub-surface anomaly in typically correlated gravity fields using observations of elements of the gravity gradient tensor. We also evaluated the reliability of the hypothesis testing and the associated predicted probabilities of misses and false alarms. Our simulations and statistical analyses confirm that the power of the tests increases as the signal strength increases and as more gradient tensor components per observation point are included. We also found that the hypothesis test that is designed to predict the probability of a miss is more robust and powerful than the one for predicting a false alarm. Moreover, the probability of a miss is somewhat smaller than the probability of a false alarm under otherwise equal circumstances.
Estimation of the rates of uptake of Rb86 by the heart, liver and skeletal muscle of man with and without cardiac disease.

Abstract The rate of uptake of Rb 86 from the blood by the myocardium was estimated in a group of subjects with coronary arteriosclerosis and compared to the rate in controls and in subjects with other types of heart disease. These studies were prompted by experiments in dogs which showed that the amount of coronary blood flow is probably an important determinant of the rate of uptake of Rb 86 . Two-thirds of the Rb 86 in arterial plasma is removed during one circulation through the dog's heart. The rate of Rb 86 uptake is increased by l -norepinephrine and decreased by pitressin, changes which are in the same direction as the known effects of these drugs on coronary blood flow. The rate of uptake of Rb 86 would also probably be affected by differences in the kinetics of potassium within the myocadrium, since rubidium and potassium are very similar in their biological and chemical properties. The differences in rate of uptake of Rb 86 by the myocardium in different dogs could be estimated within 20 per cent by using a scintillation counter placed over the precordium of the intact animal. This report summarizes the findings in 35 human subjects studied by methods similar to those used previously in dogs.
Modeling of the impact of source/drain regions on short channel effects in MOSFETs

This paper investigates the impact of the source/drain regions of MOSFETs on the short channel effects, by using numerical simulations as well as analytical modeling. First, the evidence of different SCEs when including or excluding S/D regions is presented using drift-diffusion simulation. It is then shown that this difference is related to the different boundary conditions used in the simulations. This different behavior is then modeled in terms of a shift in the built-in potential at the channel-S/D junction, which allows to avoid the overestimation of the SCEs, while keeping the same analytical modeling framework.
Turnover of phosphatidylglycerol in Streptococcus sanguis

Summary When S . sanguis was pulsed with [2- 3 H]glycerol for 10 min and chased for 60 min, 52% of the [ 3 H]lipids were chased into exocellular compounds (34%) in the culture medium and cold phenol-extractable cell bound complex saccharides (18%). The apparent rapid turnover of the lipid fraction was found to be due to phosphatidylglycerol. The phenol extractable compounds have been purified and characterized as lipoteichoic acids. The exocellular compounds were fractionated with a Bio-Gel P-2 column into three peaks (Pk's 1, 2 and 3, based on descending order of molecular size). Pk 1 was characterized as a lipoteichoic acid-like compound containing glycerolphosphate and possibly glucose; Pk 2 as a mixture of glycerolphosphate and a small molecular weight compound, and Pk 3 as glycerol.
Is there an effective salvage therapy for advanced Hodgkin's disease?

Summary The availability of increasing numbers of active agents has led to the development of a succession of regimens for use as alternative and second-line therapy following relapse from or refractoriness to MOPP (mechlorethamine/vincristine/procarbazine/prednisone) or its variants. ABVD (doxorubicin/bleomycin/ vinblastine/dacarbazine) has been the most widely used and has been considered non-cross-resistant. Other programs containing the nitrosourea lomustine have been used with results similar to those with ABVD. A relatively small fraction of relapsed patients remain failure free at 5 years (about 20% to 30%) despite a 30% to 60% second-line complete response (CR) rate. The few randomized trials (Cancer and Leukemia Group B [CALGB], European Organization for Research and Treatment of Cancer) evaluable to assess the efficacy of alternating MOPP/ABVD compared with MOPP alone have shown a small but significant advantage in freedom from progression and/or survival favoring the complex regimens over MOPP. The CALGB trial (8251) included a third arm of ABVD alone. The ABVD and MOPP/ABVD arms had a higher CR rate and superior failure-free survival (FFS) than did MOPP, but have thus far shown no difference between ABVD and alternating MOPP/ABVD, suggesting that full doses of a single regimen are equivalent to the more complex multidrug regimen. The next step in the CALGB program was to attempt to improve ABVD. The substitution of etoposide, an active single agent, for dacarbazine and bleomycin in ABVD resulted in a new regimen, EVA (etoposide/vinblastine/doxorubicin). This program has already demonstrated a 66% response rate in MOPP-resistant/relapsed patients (CALGB 8751). The median FFS is about 10 months and closely resembles the FFS curve of ABVD used as a crossover treatment for relapse/resistance in the MOPP alone arm of the CALGB trial mentioned above. The EVA program is without pulmonary toxicity and offers the potential for etoposide dose escalation. Future trials could compare ABVD with EVA as primary therapy, especially if ABVD is equivalent to the hybrid in the current Intergroup trial (CALGB 8952). High-dose therapy with autologous bone marrow transplantation (ABMT) or stem cell support represents intensive salvage treatment for those who fail at least two regimens. In 1989, 240 patients were reported with a CR rate of 46%, whereas 35% were continuously free of disease at 3 years. The criteria that predict a good response are as follows: 0 performance status; sensitive relapse; and failure of up to two regimens. Longer follow-up is still required to determine the final effect of ABMT.
Discriminative stimulus properties of toluene in the mouse.

Abstract Little is known about the nature of the acute intoxication produced by exposure to high concentrations of toluene such as that which occurs with spills and in solvent abusers. The intoxication may be similar to that produced by classic central nervous system depressants such as the barbiturates. To investigate this hypothesis, drug discrimination procedures were used to compare the acute effects produced by toluene and pentobarbital (PB). Mice were trained to discriminate toluene (100 mg/kg, ip) from vehicle in a two-lever task in which responding was under the control of a fixed-ratio 20 (FR20) schedule of food presentation. Generalization tests were conducted after 20-min inhalation exposures to toluene (150–3600 ppm) and 20 min after injections with either PB (5–30 mg/kg) or morphine (3–20 mg/kg). Most mice generalized to inhaled toluene and to PB in a concentration- or dose-related fashion, but not to morphine. These results show that the effects of injected toluene can be established as a discriminative stimulus in mice, and that these stimulus effects are independent of route of administration. Shared discriminative stimulus properties with PB suggest that toluene produces an acute intoxication like that of other classic CNS depressants.
SB : a new HLA-linked human histocompatibility gene defined using HLA-mutant cell lines

Although the genes of the major histocompatibility complex (MHC) are tightly linked, four loci (HLA-A, B, C and DR) have been defined using rare families in which antigenic specificities segregated from each other. As an alternative approach for defining loci, Kavathas et al.1 selected HLA-mutant lymphoblastoid cell lines (LCLs) that had lost expression of specific genetic markers. An HLA-GLO heterozygous LCL, LCL-721, was mutagenized with ionizing radiation which is known to induce multigenic deletions2; variants no longer expressing a specific HLA antigen were selected. While some mutants lost expression of only the antigen selected against, most simultaneously lost expression of several identifiable cis-linked gene products. Many of the multiple-loss mutants resulted from chromosome rearrangements, especially deletions1. Five new secondary B-cell (SB) antigens have recently been defined3,4, which evoke strong secondary allogeneic proliferative and cytotoxic responses. Because they resemble the HLA-DR antigens both functionally and genetically, it was not known whether they were coded for by a gene distinct from the gene(s) encoding HLA-DR. We have now characterized LCL-721 mutants for expression of both HLA-DR and SB. Of 20 lines which had lost expression of the HLA-A, -B and -DR antigens from one haplotype, four retained expression of the cis-linked SB antigen. One of these mutants had a visible deletion that included the region coding for HLA on the short arm of one chromosome 6. Because the cis-linked SB antigen continued to be expressed, the gene coding lor SB antigens must be different from that coding for HLA-DR antigens.
The Computer Prescription: Medical Computing, Public Policy, and Views of History:

This article traces past trends and current developments in medical computing in the United States. It suggests a link between shifts in emphases in medical computing and in federal government policy toward health care delivery. The development of medical computing was not driven solely by the internal imperatives of science and technology, but by dreams and visions of how computers could revolutionize medicine. Such dreams and visions constitute a mythical charter similar to ideologies and rhetoric used to mobilize support by other computerization movements. This mythical charter influenced development of medical computing by tying computing in medicine to policy goals. This charter also affected historical accounts in medical computing, which are characterized by technological determinism and evidence of cognitive dissonance due to failure to achieve policy goals.
Endovascular recanalization in acute ischemic stroke Regionalized organization of care

It is time to systematically plan for the next era in reperfusion therapy for acute ischemic stroke—the epoch of endovascular treatment. Reperfusion therapies for acute arterial occlusions in different organ beds naturally evolve in 2 successive eras. In the first, IV thrombolysis (IVT) launches the reperfusion age, as the first useful, widely disseminated therapy, but its success is constrained by only modest recanalization rates. Then, in the second, endovascular recanalization techniques (ERTs) are developed that are far more effective at achieving reperfusion and supersede IVT alone to become the definitive, ongoing standard of care. This 2-stage pattern characterized the evolution of reperfusion therapy for both acute myocardial ischemia and acute limb ischemia. Reflecting the greater complexity and fragility of the brain and its vasculature, the evolution of acute ischemic stroke care has been slower but now can be seen to be also traversing this same historical path. The decades from 1990 to 2010 were the era of IVT for acute ischemic stroke, as IVT evolved from untested therapy through clinical trial–validated intervention to standard therapy embedded in nationwide hospital systems of care. We are now living and working in the early phase of the era of ERTs. The initial period of rapid, iterative technologic advance has been proceeding apace, as the endovascular armamentarium has expanded from intra-arterial …
Rings whose cyclics have finite Goldie dimension

Abstract A module M is said to be weakly injective if every finitely generated submodule of its injective hull E ( M ) is contained in a submodule X of E ( M ) isomorphic to M . We prove that a ring R satisfies the property that every cyclic right R -module has finite Goldie dimension if and only if every direct sum of (weakly) injective right R -modules is weakly injective. This is analog to the well-known characterization of right Noetherian rings as those for which direct sums of injective right modules are injective.
ECM roles in the function of metabolic tissues

All metazoan cells produce and/or interact with tissue-specific extracellular matrices (ECMs). Such ECMs play important structural roles not only in connective tissues, but in all tissues in which they provide support and anchorage for cells. However, in addition to such structural roles it has become increasingly clear that the tissue-specific microenvironments formed by the ECM play instructional roles that inform the proper phenotypes and functional behaviors of specialized cell types, and recent in vivo and in vitro studies suggest that ECM components also affect metabolic function. This review summarizes data that provide insights into the roles of the ECM in informing the proper development and functioning of highly specialized cells of metabolic tissues, such as adipocytes and islet β cells.
Rating the severity and character of transient cocaine-induced delusions and hallucinations with a new instrument, the Scale for Assessment of Positive Symptoms for Cocaine-Induced Psychosis (SAPS-CIP).

Abstract Background: Cocaine can induce transient psychotic symptoms. We examined the phenomenology of such cocaine-induced psychosis (CIP) using a modified version of the Scale for Assessment of Positive Symptoms (SAPS), a well-validated instrument for the assessment of schizophrenic psychosis. Methods: We developed a new instrument, the Scale for Assessment of Positive Symptoms for Cocaine-Induced Psychosis (SAPS-CIP), based on the well-validated SAPS. We interviewed 243 unrelated cocaine-dependent adults using both the SAPS-CIP and an instrument for the identification of cocaine-induced paranoia, the Cocaine Experience Questionnaire (CEQ). Results: One hundred and eighty-one (75%) of the subjects endorsed CIP using the CEQ. With the SAPS-CIP, hallucination (HAL) and delusion (DEL) scores correlated strongly, and the DEL domain showed excellent concurrent validity with the CEQ. We observed significant positive correlations, respectively, between severity of HAL and DEL, and lifetime number of episodes of cocaine use, and negative correlations with age at onset of cocaine use. Conclusions: The results suggest that CIP consists of transient delusional and hallucinatory symptoms, which tend to occur together and co-vary in severity. It appears that rating cocaine-induced paranoia alone (e.g., with the CEQ) can identify most subjects experiencing CIP. However, the SAPS-CIP is useful for quantifying the severity of CIP according to operational criteria. Our data provide additional evidence that CIP is a sensitizing response.
Investigation of the Influence of FcRn on the Distribution of IgG to the Brain

It has been suggested that the neonatal Fc receptor (FcRn) is a primary determinant of the distribution of IgG to the brain. In the present report, 125I-labeled 7E3, a monoclonal IgG1 antibody, was injected intravenously to groups of FcRn-deficient mice and C57BL/6J control mice. Sub-groups of three mice were sacrificed at several time points. Blood and brain tissue were harvested and radioactivity was assessed. Antibody concentrations in brain were corrected for residual blood using 51Cr-labeled red blood cells. Data were analyzed via WinNonlin, and areas under plasma and tissue concentration vs. time curves (AUCs) were assessed via the Bailer method. The apparent plasma elimination half-life and clearance of 7E3 were 13.61 ± 0.61 days and 6.5 ± 0.10 ml/day/kg in control mice and 0.70 ± 0.05 days and 63.5 ± 2.7 ml/day/kg in the knockout mice. Plasma and brain AUCs (0–10 days) were found to be 3,338.7 ± 50.4 and 7.46 ± 0.5 nM day in control animals and 781.2 ± 16.6 and 1.65 ± 0.1 nM day in FcRn-deficient animals. There was no significant difference between brain-to-plasma AUC ratios in control and FcRn-deficient mice (0.0022 ± 0.00015 vs. 0.0021 ± 0.00011, p = 0.3347). Two-way analysis of variance showed no significant differences, at any time point, between brain-to-plasma concentration ratios determined from control and knockout animals. The results suggest that FcRn does not contribute significantly to the “blood–brain barrier” for IgG in mice, and the data suggest that FcRn is not responsible for the low exposure of IgG in the brain relative to plasma.
Generation of a nucleosome-free promoter region in SV40 does not require T-antigen binding to site I.

Abstract The relationship between T-antigen interactions at Site I and the presence of a nucleosome-free promoter in SV40 chromatin was examined by analyzing chromatin from mutants defective for T-antigen interaction at site I (cs1085, scs1 11, and tsA58) and their parental wild-type strains (776, SVS, and VA45–54, respectively). As judged by sensitivity to digestion with restriction endonucleases that recognize unique sequences within the promoter region ( Bg /I, Kpn I, and Msp I), a nucleosome-free promoter was observed in a substantially larger proportion of chromosomes from the defective mutants than their wild-type parents. This result demonstrates that T-antigen binding to site I is not necessary for setting the early boundary of the nucleosome-free region, although it may function directly or indirectly in determining the proportion of chromosomes containing this feature.
Estimating ankle rotational constraints from anatomic structure

Three-dimensional biomedical data obtained through tomography provide exceptional views of biological anatomy. While visualization is one of the primary purposes for obtaining these data, other more quantitative and analytic uses are possible. These include modeling of tissue properties and interrelationships, simulation of physical processes, interactive surgical investigation, and analysis of kinematics and dynamics. As an application of our research in modeling tissue structure and function, we have been working to develop interactive and automated tools for studying joint geometry and kinematics. We focus here on discrimination of morphological variations in the foot and determining the implications of these on both hominid bipedal evolution and physical therapy treatment for foot disorders.© (1992) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Some Simple Distribution-Free Confidence Intervals for the Center of a Symmetric Distribution

Abstract A family of confidence intervals with endpoints that are simple averages of sample order statistics is defined. In this family the interval with shortest expected length is selected and compared to other confidence intervals for the same parameter.
Nonconvulsive Status Epilepticus: EEG Analysis in a Large Series

We analyzed EEG characteristics comprehensively in a large series of nonconvulsive status epilepticus (NCSE) cases. Eighty-five ictal episodes in 78 patients were analyzed. The ictal discharges were generalized (group G) in 59 episodes (69%), diffuse with focal predominance (group GF) in 15 (18%), and focal (group F) in 11 (13%). The morphologies and patterns of persistence varied greatly. Frequency of ictal discharge was also variable and was almost always < 3 Hz. Demonstration of focal epileptic features in response to intravenous (i.v.) diazepam (DZP) and the presence of interictal focal epileptiform discharges in some cases in groups G and GF suggested possible focal onset secondarily generalized in these cases. This study suggests that electrographically NCSE is a highly heterogeneous epileptic state, and i.v. DZP may serve as a valuable diagnostic tool in differentiating generalized from focal onset NCSE.
Synthesis and anti-HIV activities of bis-(cycloSaligenyl) pronucleotides derivatives of 3′-fluoro-3′-deoxythymidine and 3′-azido-3′-deoxythymidine

Anti-HIV nucleoside monophosphates have limited cellular uptake due to the presence of negatively-charged phosphate group. Bis-(cycloSaligenyl) derivatives containing two anti-HIV nucleosides, 3'-fluoro-3'-deoxythymidine (FLT) and 3'-azido-3'-deoxythymidine (AZT) were synthesized to increase intracellular delivery of nucleoside monophosphates. 2,5-Bis(hydroxymethylene)benzene-1,4-diol was selected as a monocyclic bidentate scaffold and synthesized by three different methods from bis(hydroxymethylene)cyclohexan-1,4-diene-1,4-diol, or diethyl 2,5-dihydroxyterephthalate. The reaction of the tetraol with diisopropylphosphoramidous dichloride in the presence of 2,6-lutidine, followed by conjugation reactions with nucleosides (i.e., FLT and AZT) and oxidation afforded symmetrical and unsymmetrical bis-(cycloSaligenyl) diphosphate triester products, AZT-AZT, FLT-FLT, and FLT-AZT conjugates, in 63-74% overall yields and modest anti-HIV activities (IC50 = 2.8-69.6 µM).
Separability and triangulated categories

Abstract We prove that the category of modules over a separable ring object in a tensor triangulated category admits a unique structure of triangulated category which is compatible with the original one. This applies in particular to etale algebras. More generally, we do this for exact separable monads.