cssi/SciSciGPT-SciSciNet huggingface dataset:
An Open, Phase III Study of Lanreotide(Somatuline PR) in the Treatment of Acromegaly.

Acromegaly is a disorder caused by excessive secretion of human growth hormone (GH). Somatostatin and its analogue-prolonged release formulation, lanreotide (Somatuline PR), inhibit the secretion of growth hormone. The aim of this open Phase III study was to investigate the clinical efficacy of lanreotide in the treatment of six acromegalic patients with a mean age of 44 +/- 13 yr including two patients with diabetes mellitus. All the patients previously received transsphenoidal or transcranial hypophysectomy. Lanreotide was given intramuscularly every 2 weeks at a fixed dose of 30 mg for 12 weeks. Serum GH and insulin-like growth factor-I (IGF-I) levels were evaluated before, 2, 6 and 12 weeks after treatment. After 12 weeks of treatment, mean (+/- SEM) GH levels decreased from 24.8 +/- 12.5 to 6.9 +/- 3.3 ng/ml and mean serum IGF-I levels decreased from 689 +/- 282 to 430 +/- 216 ng/ml. Abdominal ultrasonographic examinations showed no gallbladder stone or bile sand formation before or after the treatment. Three of the patients who did not receive octreotide presented with manifestations of mild gastrointestinal adverse effect such as mild abdominal pain and diarrhea. In conclusion, lanreotide is effective in the treatment of active postoperative acromegaly.
A1-adenosine receptor inhibition of adenylate cyclase in failing and nonfailing human ventricular myocardium.

BACKGROUNDReceptors that couple via the stimulatory G protein, Gs, to adenylate cyclase and to a positive inotropic response have been extensively investigated in falling human heart. In contrast, much less is known about receptors, such as the A1-adenosine receptor, that couple to adenylate cyclase via the inhibitory G protein, Gi, to give a negative inotropic response. Activation of such Gi-coupled receptors might worsen heart failure. Furthermore, alpha Gi is increased in failing human ventricular myocardium, which may enhance inhibitory receptor coupling to adenylate cyclase.METHODS AND RESULTSA1-Adenosine receptor inhibition of adenylate cyclase was examined in crude particulate preparations derived from 12 nonfailing and 12 failing human left ventricles. Experimental conditions were designed for maximal inhibitory responses. Dose-response curves were performed with the selective A1-adenosine receptor agonist R-phenylisopropyl-adenosine (R-PIA). No differences in nonfailing versus failing heart were ...
Recent developments in our understanding of sepsis : evaluation of anti-endotoxin antibodies and biological response modifiers

Sepsis and septic shock are among the most frequent life-threatening infectious disease problems encountered in emergency medicine practice. This review summarizes the extensive research into the pathophysiology of sepsis, with emphasis on Gram-negative infection. Particular reference is given to the exogenous and endogenous mediators involved in the sepsis cascade. It also critically evaluates new preparations developed to blunt the actions of the exogenous and endogenous mediators responsible for the clinical manifestations comprising this syndrome. Clinical signs likely to be associated with Gram-negative infection are also reviewed, and guidelines are considered for the potential use of newly developed anti-endotoxin antibodies and other biological response modifiers in the treatment of patients with Gram-negative sepsis.
Fixed versus variable-parameter matrix models of forest growth: the case of maple-birch forests

Abstract A matrix growth model with constant parameters has been modified, by making survivor growth and mortality of trees functions of stand basal area. The functions, estimated from re-measured plots in Wisconsin maple-birch forests, showed that basal area affected mostly the growth of small trees. However, even when the effects were statistically significant, they were small. Fifteen-year forecasts with the variable-parameter model were almost identical to those of the fixed-parameter model for a set of 37 random plots. Long-term, steady-state predictions gave similar diameter distributions for both models, but a 20% lower basal area for the variable-parameter model. Steady-state management regimes that maximized soil rent were identical for both models in terms of intensity of harvest and length of cutting cycle. The basal area, harvests, and net present values predicted by both models, in the long run and during conversion, were also nearly the same. For managed maple-birch forests, the matrix model with constant parameters has the advantage of simplicity of form, estimation, and application, especially in optimization mode.
Mutational analysis of tetracycline resistance protein transmembrane segment insertion.

The tetracycline resistance proteins (TetA) of gram-negative bacteria are secondary active transport proteins that contain buried charged amino acids that are important for tetracycline transport. Earlier studies have shown that insertion of TetA proteins into the cytoplasmic membrane is mediated by helical hairpin pairs of transmembrane (TM) segments. However, whether helical hairpins direct spontaneous insertion of TetA or are required instead for its interaction with the cellular secretion (Sec) machinery is unknown. To gain insight into how TetA proteins are inserted into the membrane, we have investigated how tolerant the class C TetA protein encoded by plasmid pBR322 is to placement of charged residues in TM segments. The results show that the great majority of charge substitutions do not interfere with insertion even when placed at locations that cannot be shielded internally within helical hairpins. The only mutations that frequently block insertion are proline substitutions, which may interfere with helical hairpin folding. The ability of TetA to broadly tolerate charge substitutions indicates that the Sec machinery assists in its insertion into the membrane. The results also demonstrate that it is feasible to engineer charged residues into the interior of TetA proteins for the purpose of structure-function analysis.
Computational Studies on Detecting a Diffusing Target in a Square Region by a Stationary or Moving Searcher

In this paper, we compute the non-detection probability of a randomly moving target by a stationary or moving searcher in a square search region. We find that when the searcher is stationary, the decay rate of the non-detection probability achieves the maximum value when the searcher is fixed at the center of the square search region; when both the searcher and the target diffuse with significant diffusion coefficients, the decay rate of the non-detection probability only depends on the sum of the diffusion coefficients of the target and searcher. When the searcher moves along prescribed deterministic tracks, our study shows that the fastest decay of the non-detection probability is achieved when the searcher scans horizontally and vertically.
Two-dimensional polyacrylamide gel electrophoresis of bovine semen after cryopreservation in half- milliliter straws

Abstract One of the problems encountered with two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) is the streaking of proteins so that individual spot identification is compromised. This study was conducted to determine whether a low loading dose (50μg) of protein would permit resolution of more discrete protein spots using megapixel camera technology, and if so, to present a nomenclature for future comparisons of the identified proteins. If the major proteins could be identified in a 50-μg sample we aimed to determine whether they could be identified in the supernatant (seminal plasma plus extender) of cryopreserved semen. Two ejaculates were obtained from each of 6 bulls and bovine seminal plasma (BSP) protein concentration was standardized to 50μg/10μl. Isoelectric points (pI) and molecular weights (MWt) of BSP proteins were determined by measuring spot mobility on 2-D PAGE (15% polyacrylamide). Three distinct protein spot constellations (a,b,c) could be readily seen by the naked eye and a faintly stained constellation “d” was identified by the megapixel camera. The image analysis software located 6 protein spots in both constellation “a” (MWt 26 kDa; pI 4.2 to 4.8) and “b” ( MWt 27 kDa; pI 6.6 to 8.0). Constellation “c” contained 13 protein spots distributed in a right-angled triangle with its base towards the acidic end of the gel (MWt 14.7 to 18.8 kDa; pI 5.3 to 7.4). Only spots c2, c3, c5, c8, and c13 were present in all 12 samples. Streaking can be eliminated by using 50μg protein for 2-D PAGE, and the major protein spots are readily identified by megapixel camera technology. Protein spots c3, c5, c13 and constellation “a” appear to correspond with Manjunath's proteins (BSP-A1, -A2; -A3; -30kDa). Killian's 2 low fertility proteins may lie in the “c” constellation, and 1 of the high fertility proteins may lie in the “b” constellation. The 3 major BSP proteins can be visualized in the supernatant of cryopreserved semen. We believe that the technique may prove useful for retrospective analysis of processed semen batches that achieve less than satisfactory results in the field.
Iatrogenic Cervical Deformity

Iatrogenic deformities of the cervical spine are not uncommon and may be associated with either anterior or posterior operations. To minimize the “footprints” left behind from surgical interventions on the cervical spine, it is imperative not only to treat the present disorder but also avoid sowing the seeds of future problems, or at least create a milieu in which they can be easily addressed should they occur. Doing so requires attention to either correcting or preventing cervical deformities whenever possible during the index operation because the optimal method of treating iatrogenic cervical deformity remains its prevention. In treating established deformities, surgical decision making hinges on whether the deformity is rigid, flexible, or fused.
Patterns of estuarine use by juvenile English sole ( Parophrys vetulus ) and Dungeness crab ( Cancer magister )

Extensive trawl surveys were conducted in two large estuaries (Grays Harbor and Willapa Bay) on the Washington coast during 1983–1987, and in adjacent areas of the open coast. These surveys have shown that both English sole and Dungeness crab rely heavily on these estuaries as nursery areas, although the pattern of utilization differs substantially. Juvenile migration patterns can show substantial interannual variability and can only be delineated by concurrent surveys in both coastal and estuarine areas, conducted over a period of several years. English sole eggs and Dungeness crab larvae are released in coastal waters. Larvae of both species transform to the benthic stage in both coastal and estuarine areas, but most English sole eventually migrate into the estuaries during the first year of life, even if initial settlement is along the open coast. By the time English sole have attained a length of 55 mm (TL), most of them are found in estuaries. English sole begin emigrating from the estuaries at about 75 mm, and few remain there during the second year of life. In contrast, Dungeness crab appear to remain in the area of initial settlement throughout the first year of life. Growth is substantially faster in estuaries where 0+ crab reach a mean size of about 40 mm carapace width (CW) by September, with those off the coast are only about 14 mm CW. Juveniles remain in the area of settlement over their first winter but, in contrast to English sole, most coastal 1+ crab immigrate to estuaries to join siblings that settled there the previous year. By September of the second year, crab at about 100 mm CW emigrate to the open coast where they reach maturity. Advantages to juvenile stages that reside in estuaries are discussed in terms of accelerated growth at higher temperatures and potentially greater food supplies than found nearshore along the coast.
Schizophrenia and the Hippocampus: The Embryological Hypothesis Extended

Recent studies suggest that consistent structural changes exist in the hippocampi of schizophrenic patients. These alterations are characterized by a significant degree of disorientation of the hippocampal pyramidal cells when compared with age-matched nonschizophrenic controls. The degree of neuronal disorientation seems to correlate positively with the severity of the clinical picture. A hypothesis on the pathogenesis of this process, suggested in an earlier article, is extended here. Putative maternal infection with one of several neuraminidase-bearing viruses, especially during the second trimester of pregnancy, may severely affect the migration of primitive neurons into the primordial hippocampus. The "neuraminidase effect," expressed through alteration of the normal sequential patterns of N-CAM (neuronal-cell adhesion molecule) maturation, may result in the cellular disarray we have noted. This alteration may prove useful as a cell marker for schizophrenia, even though its actual relation to clinical symptomatology has still to be evaluated. Genetic factors also are believed to be involved, perhaps in the form of certain patterns of reduced immunocompetence, which might render the mother more susceptible to viral infection.
Reactivity to in vivo marijuana cues among cannabis-dependent adolescents.

Abstract Introduction Cannabis dependence is a common but poorly understood condition in adolescents. Marijuana craving has been posited as a potential contributing factor to continued use and relapse, but relatively few studies have focused on the measurement of craving and reactivity to marijuana cues. The present work sought to explore reactivity to marijuana cues within this age group. Methods Thirty treatment-seeking cannabis-dependent adolescents (age 13–20) completed a cue reactivity session, consisting of exposure to and manipulation of in vivo marijuana cues (“joint” and lighter) and matching neutral cues (pencil and eraser), in counterbalanced order. Subjective craving and physiological reactivity were assessed. Results Participants demonstrated increased craving and skin conductance reactivity in response to marijuana cues, relative to neutral cues. Conclusion In vivo marijuana cues appear to elicit significant subjective and physiological reactivity among treatment-seeking cannabis-dependent adolescents. Further work is needed with a larger sample and with a wider variety of cues.
The relationship between parkinson syndrome and vascular siderosis: An electron microprobe study

Vascular siderosis (VS) refers to the presence of mineralized small and medium-sized arteries in the globus pallidus, usually regarded as reflecting an aging process. The electron probe analysis of deposits in vascular siderosis in 10 patients dying of parkinsonism and in 8 other patients without parkinsonism is reported here. The microprobes identified a total of 11 elements in the VS in these 18 patients. Five elements—lead, aluminum, sulfur, manganese, and barium—were present only in VS associated with parkinsonism. Statistically, the association of lead was highly significant while that of aluminium and sulfur was only suggestive. Lead was present in 7 of the 10 patients with parkinsonism and aluminium and sufur in 4. The significance of the presence of sulfur is difficult to assess since its compounds are normally present in large quantities in the brain. These findings raise the question whether lead and aluminum may be associated in some way with the pathogenesis of certain forms of Parkinson disease.
Measuring and Explaining Charge Bargaining

Charge bargaining is a potentially important form of discretion in criminal sentencing that is obscured in many studies of sentencing outcomes. Our procedure to measure the difference in sentencing outcomes caused by plea bargain emphasizes the amount, in months, that the sentence length is reduced. Using this measure, we compare prosecutorial discretion across counties in two different states. We conclude that charge bargaining plays an empirically important role in determining sentencing outcomes. Furthermore, we find that measuring the distance (in months of prison time) moved during a charge bargain may provide a very different estimate of the discretion than is given by the rate of bargaining, which is the usual measure used. Although the rate of charge bargaining was higher in the voluntary guidelines state, its impact on sentences was greater in the presumptive guidelines jurisdiction, as predicted by Reitz (1998). We further observe a dramatic difference in predictions from shifting the case characteristics underlying the summary measure. This result reveals that distributional differences (either due to the underlying criminal activity or due to the overall level of severity of punishment) can easily obscure the inferences necessary for understanding the operation of the systems. Our finding of differential charge bargaining in these two jurisdictions should provide a caution when comparing the results of studies of disparity in sentencing across jurisdiction types.
Treatment of depressed-maritally discordant individuals: Is there a psychological treatment of choice?

Since Coyne’s (1976) seminal paper on the interpersonal aspects of depression, the importance of marital processes in depression increasingly has moved to center stage in clinical conceptualization and theory. Marital discord and depression are clearly linked (Beach, Sandeen & O’Leary, 1990), and problematic relationships are often central to the development and course of depression (cf. Coyne & Downey, 1991). This central fact is being increasingly recognized by disparate groups with varying agendas, but a common interest in advancing the quality of mental health care. The final report of the American task force on women and depression highlighted the role of interpersonal processes, particularly transactions occurring within intimate relationships, in the pathogenesis of depression for women (McGrath, Keita, Strickland, & Russo, 1990). Unhappy marriages have been shown to pose a major risk for the development of unipolar depression (Weissman, 1987). It has been reported that simply being married is a predictor of slower recovery from a depressive episode (George, Blazer, Hughes, & Fowler, 1989), married persons do more poorly on antidepressant medication than do others (Keller et al., 1984), and being maritally discordant is a predictor of relapse following pharmacological treatment for depression (Hooley & Teasedale, 1989). A decade ago one might have asked if marital or family interventions had anything to add to the more commonly used individual and somatic approaches. Indeed, some centers specializing in the treatment of depression did not even systematically assess for the presence or severity of marital problems. However, one is now more likely to be confronted with the assertion that marital therapy for depressed-discordant individuals is “common sense.” Indeed, in discussions with clinical colleagues, some have expressed concern that when individual work or pharmacotherapy is done in the context of marital discord and depression it
Refereed Papers: Alternative Method for Unique RSA Primes Generation

This paper describes a new method for generating RSA primes. While the primes generated according to this method satisfy all of the existing requirements for making RSA encryption and signature generation secure and efficient, they possess two additional properties. First, the RSA primes derived by different parties will always be different. This is a highly desirable property in view of possible disputes around the authenticity of a digital signature. Second, it will not be necessary to store any seed values to verify that these primes were generated according to the prescribed procedure. This is achieved by incorporating the required information about the seeds into the primes themselves without weakening the security properties of the RSA primes.
Laptops in the classroom

This paper focuses on a rapidly growing population on many college and university campuses today: students equipped with laptop computers capable of wireless connection to the Internet. More and more departments are requiring that students enrolling in certain courses bring laptop computers to class. The course instructor is sometimes overwhelmed by the prospect, asking "How should I change my lesson plan in order to integrate the laptop in my daily lecture?" This paper first describes the effort to bring the laptop to campus at a number of colleges and universities around the country. It then offers concrete suggestions based on the experiences of several professors who either have taught, or are now teaching, laptop-required courses. The paper concludes with a summary and a look toward the future.
SOFT-TISSUE INJURIES AND MUSCLE TEARS

Soft-tissue injuries and muscle tears occur frequently in athletes. The mainstay of treatment in most cases is nonoperative management and aggressive rehabilitation. Most injuries result from direct trauma or contusion or indirect stretch injury. It is important to keep in mind the possibility of other potentially more serious conditions, such as compartment syndrome. More research is needed to define optimal treatment patterns and potential strategies for injury prevention.
Thermo-fluid dynamic design study of single and double-inflow radial and single-stage axial steam turbines for open-cycle thermal energy conversion net power-producing experiment facility in Hawaii

The results of the study of the optimum thermo-fluid dynamic design concept are presented for turbine units operating within the open-cycle ocean thermal energy conversion (OC-OTEC) systems. The concept is applied to the first OC-OTEC net power producing experiment (NPPE) facility to be installed at Hawaii's natural energy laboratory. Detailed efficiency and performance calculations were performed for the radial turbine design concept with single and double-inflow arrangements. To complete the study, the calculation results for a single-stage axial steam turbine design are also presented. In contrast to the axial flow design with a relatively low unit efficiency, higher efficiency was achieved for single-inflow turbines. Highest efficiency was calculated for a double-inflow radial design, which opens new perspectives for energy generation from OC-OTEC systems.
Follow-up evaluation after renal artery bypass surgery with use of carbon dioxide arteriography and color-flow duplex scanning

Abstract Purpose: Postoperative evaluation of renal artery bypass grafts historically has been obtained by contrast renal arteriography before discharge from the hospital. Recent reports have advocated replacing arteriography with abdominal duplex scanning for evaluating and monitoring the integrity of renal artery bypasses. We propose a combination of these two techniques, which provides minimal risk to the patient and renal parenchymal function. Purpose: Between July 1, 1990, and Dec. 31, 1991, 17 patients (8 men, 9 women) underwent 24 renal artery bypasses for poorly controlled hypertension or deteriorating renal function. In the immediate postoperative period each patient underwent carbon dioxide (CO2) renal arteriography to detect any technical defects and to define bypass graft anatomy. Subsequently, color-flow duplex scanning of the renal artery bypass grafts were done at 3-month intervals with the postoperative CO2 arteriogram for baseline comparison. CO2 arteriography clearly defined proximal/distal anastomotic anatomy, bypass conduit integrity, and bypass conduit runoff. Results: Procedural morbidity was zero because no hematomas developed and serum creatinine remained stable. Duplex scanning for a mean follow-up of 8.3 months revealed antegrade flow in 23 bypasses with peak systolic velocity of 60 to 100 cm/sec. One bypass graft had a peak systolic velocity greater than 150 cm/sec suggestive of a proximal anastomotic stenosis; however, the patient died before a repeat, verifying CO2 arteriogram could be obtained. Recurrent hypertension developed in one patient with velocities less than 100/cm/sec, and repeat CO2 arteriography revealed no evidence of graft or anastomotic stenosis. Conclusion: CO2 arteriography and duplex scanning provide an accurate means of initially evaluating and subsequently monitoring renal artery bypass grafts, with minimal risk of renal or patient morbidity. (J V ASC S URG 1993;18:23-30.)
Categorizing and extracting information from multilingual HTML documents

The amount of online information written in different natural languages and the number of non-English speaking Internet users have been increasing tremendously during the past decade. In order to provide high-performance access of multilingual information on the Internet, we have developed a data analysis and querying system (DatAQs) that: (i) analyzes, identifies, and categorizes languages used in HTML documents; (ii) extracts information from HTML documents of interest written in different languages; (iii) allows the user to submit queries for retrieving extracted information in the same natural language provided by the query engine of DatAQs using a menu-driven user interface; and (iv) processes the user's queries (as Boolean expressions) to generate the results. DatAQs extracts information from HTML documents that belong to various data-rich, narrow-in-breadth application domains, such as car ads, house rentals, job ads, stocks, university catalogs, etc. The average F-measure on identifying HTML documents written in a particular natural language correctly is 89%, whereas the F-measure on categorizing HTML documents belonged to the car-ads application domain is 94%.
Geminin stabilizes Cdt1 during meiosis in Xenopus oocytes.

During the mitotic cell cycle, Geminin can act both as a promoter and inhibitor of initiation of DNA replication. As a promoter, Geminin stabilizes Cdt1 and facilitates its accumulation leading to the assembly of the pre-replication complex on DNA. As an inhibitor, Geminin prevents Cdt1 from loading the mini-chromosome maintenance complex onto pre-replication complexes in late S, G2, and M phases. Here we show that during meiosis Geminin functions as a stabilizer of Cdt1 promoting its accumulation for the early division cycles of the embryo. Depletion of Geminin in Xenopus immature oocytes leads to a decrease of Cdt1 protein levels during maturation and after activation of these oocytes. Injection of exogenous recombinant Geminin into the depleted oocytes rescues Cdt1 levels demonstrating that Geminin stabilizes Cdt1 during meiosis and after fertilization. Furthermore, Geminin-depleted oocytes did not replicate their DNA after meiosis I indicating that Geminin does not act as an inhibitor of initiation of DNA replication between meiosis I and meiosis II.
Over-expression of the p110β but not p110α isoform of PI 3-kinase inhibits motility in breast cancer cells

Phosphoinositide 3-kinase (PI 3-kinase) activity is required for growth factor-induced cytoskeletal regulation and cell migration. We previously found that in MTLn3 rat adenocarcinoma cells, EGF-stimulated induction of actin barbed ends and lamellipod extension specifically requires the p85/p110α isoform of PI 3-kinase. To further characterize signaling by distinct PI 3-kinase isoforms, we have developed MTLn3 cells that transiently or stably overexpress either p110α or p110β. Transient overexpression of p110β inhibited EGF-stimulated lamellipod extension, whereas p110α-transfected cells showed normal EGF-stimulated lamellipod extension. Similar results were obtained by overexpression of kinase-dead p110β, suggesting that effects on cytoskeletal signaling were due to competition with p85/p110α complexes. Stable overexpression of p110α appeared to be toxic, based on the difficulty in obtaining stable overexpressing clones. In contrast, cells expressing a 2-fold increase in p110β were readily obtainable. Interestingly, cells stably expressing p110β showed a marked inhibition of EGF-stimulated lamellipod extension. Using computer-assisted analysis of time-lapse images, we found that overexpression of p110β caused a nearly complete inhibition of motility. Cells overexpressing p110β showed normal activation of Akt and Erk, suggesting that overall PI 3-kinase signaling was intact. A chimeric p110 molecule containing the p85-binding and Ras-binding domains of p110α and the C2, helical, and kinase domains of p110β, was catalytically active yet also inhibited EGF-stimulated lamellipod extension. These data highlight the differential signaling by distinct p110 isoforms. Identification of effectors that are differently regulated by p110α versus p110β will be important for understanding cell migration and its role in metastasis. Cell Motil. Cytoskeleton 59:180–188, 2004. © 2004 Wiley-Liss, Inc.
Alterations in Intestinal Microbiota Correlate With Susceptibility to Type 1 Diabetes

We tested the hypothesis that alterations in the intestinal microbiota are linked with the progression of type 1 diabetes (T1D). Herein, we present results from a study performed in subjects with islet autoimmunity living in the U.S. High-throughput sequencing of bacterial 16S rRNA genes and adjustment for sex, age, autoantibody presence, and HLA indicated that the gut microbiomes of seropositive subjects differed from those of autoantibody-free first-degree relatives (FDRs) in the abundance of four taxa. Furthermore, subjects with autoantibodies, seronegative FDRs, and new-onset patients had different levels of the Firmicutes genera Lactobacillus and Staphylococcus compared with healthy control subjects with no family history of autoimmunity. Further analysis revealed trends toward increased and reduced abundances of the Bacteroidetes genera Bacteroides and Prevotella, respectively, in seropositive subjects with multiple versus one autoantibody. Canonical discriminant analysis suggested that the gut microbiomes of autoantibody-positive individuals and seronegative FDRs clustered together but separate from those of new-onset patients and unrelated healthy control subjects. Finally, no differences in biodiversity were evident in seropositive versus seronegative FDRs. These observations suggest that altered intestinal microbiota may be associated with disease susceptibility.
Strategic Regulatory Evaluation and Endorsement of the Hollow Fiber Tuberculosis System as a Novel Drug Development Tool

The first nonclinical drug development tool (DDT) advanced by the Critical Path to TB Drug Regimens (CPTR) Initiative through a regulatory review process has been endorsed by leading global regulatory authorities. DDTs with demonstrated predictive accuracy for clinical and microbiological outcomes are needed to support decision making. Regulatory endorsement of these DDTs is critical for drug developers, as it promotes confidence in their use in Investigational New Drug and New Drug Application filings. The in vitro hollow fiber system model of tuberculosis (HFS-TB) is able to recapitulate concentration-time profiles (exposure) observed in patients for single drugs and combinations, by evaluating exposure measures for the ability to kill tuberculosis in different physiologic conditions. Monte Carlo simulations make this quantitative output useful to inform susceptibility breakpoints, dosage, and optimal combination regimens in patients, and to design nonclinical experiments in animal models. The Pre-Clinical and Clinical Sciences Working Group within CPTR executed an evidence-based evaluation of the HFS-TB for predictive accuracy. This extensive effort was enabled through the collaboration of subject matter experts representing the pharmaceutical industry, academia, product development partnerships, and regulatory authorities including the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). A comprehensive analysis plan following the regulatory guidance documents for DDT qualification was developed, followed by individual discussions with the FDA and the EMA. The results from the quantitative analyses were submitted to both agencies, pursuing regulatory DDT endorsement. The EMA Qualification Opinion for the HFS-TB DDT was published 26 January 2015 (available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000319.jsp).
Lending a hand to labor : James Myers and the Federal Council of Churches, 1926-1947

La plupart des historiens ont ignore le protestantisme comme source d'appui pour un unionisme industriel naissant, alors qu'ils reconnaissaient les importantes contributions du catholicisme au mouvement ouvrier du temps de la Depression. Pourtant un groupe important de membres du clerge protestant, invoquant l'Evangile Social, se sont personnellement engages dans la lutte pour promouvoir l'organisation du travail. Cet article cherche a elargir la comprehension de l'interaction de la religion et du syndicalisme pendant les annees trente en explorant les contributions d'un de ces membres du clerge, James Myers.
Characterization of solid state array cameras for the mid-IR

We present a characterization of some processes affecting the performance of solid state array cameras designed for ground based astronomical imaging in the 8–13μm atmospheric window. Our discussion includes a novel model for electron-hole generationrecombination noise based on the probable pathlength of an electron in a photoconductor. We use the Berkeley mid-IR Array Camera as an example. For this camera, the results show that the total optical system composed of the camera, a 3m telescope, and the atmosphere has an efficiency of about 3%, a 1σ noise equivalent flux density of 25 mJy min−1/2arcsec−2 measured over a Δλ/λ=10% band width, and a noise equivalent expressed as the ambient temperature thermal black body noise of 23%.
Management of Erectile Dysfunction After Radical Prostatectomy

Erectile dysfunction (ED) is one of the most common sequelae after radical prostatectomy for organ-confined prostate cancer. Despite nerve-sparing techniques, surgical neurovascular injury occurs and subsequent cessation of erections leads to significant cavernosal hypoxia with attendant microstructural consequences and severe impairment of erectile function (EF). Pharmacological strategies for rehabilitation of natural EF using on demand or daily phosphodiesterase type 5-inhibitors (PDE5i) have not proven to positively impact the return of unassisted EF in randomized controlled trials.
Strain differences among rats initiating exploration of differing environments

Latencies for emerging from the home cage were obtained in familiar and in strange surroundings for 557 rats from 12 inbred strains: ACI, A990 A35322, F344, INR, IR, MNR, MNR-a, MR, TS1, TS3, WAG. Significant strain effects, condition effects, and genetic-enviromental interaction were found.
Students' colleges and achievement in an advanced course.

The aim of the present study was to determine whether a significant relationship exists between a student’s college (Allied Health, Arts and Science, Education, and Graduate School) and achievement...
Synthesis of bisindolylmaleimides related to GF109203x and their efficient conversion to the bioactive indolocarbazoles

From a structure–activity relationship perspective, the new indolocarbazoles 11 and 12 have been synthesized and evaluated biologically as novel Chk1 inhibitors. Compounds 11 and 12 were synthesized in high yield from indole via bisindolylmaleimides 18 and 24.
Magnetostatic Spin-Wave Modes in Ferromagnetic Tube

Magnetostatic spin-wave modes were excited and detected in micron size ferromagnetic Co90Ta5 Zr5 rectangular tubes that wrapped around the shorted ends of coplanar waveguides. The observed modes can be assigned to surface spin waves of an infinite ferromagnetic film but with periodic boundary conditions and quantized wave vector imposed by the finite circumference of the tube.
Models of Drug Addiction

“The existence of the many contradictory theories as to needed remedial procedures appeared to be due to pronounced disagreement as to the actual nature of the problem.”–Terry and Pellens, The Opium Problem, 1928.
A Unified Flow Control Method for Loading, Routing, and Dispatching in Manufacturing Systems to Achieve Near-Zero Work-In-Process

We have developed a continuous flow (fluid) model for loading, routing, and dispatching of parts in a manufacturing system with several machines and part types. The resulting continuous control solution is used in a simple feedback scheme to determine the actual (discrete) loading, routing, and dispatching decisions. In several example where we applied this method, queues were reduced to nearly zero for demands that were very close to the capacity of the system.
Personal Digital Assistant Applications for the Healthcare Provider

OBJECTIVE:To review some common medical applications available for personal digital assistants (PDAs), with brief discussion of the different PDA operating systems and memory requirements. Key search terms included handheld, PDA, personal digital assistants, and medical applications.DATA SOURCES:The literature was accessed through MEDLINE (1999–August 2002). Other information was obtained through secondary sources such as Web sites describing common PDAs.DATA SYNTHESIS:Medical applications available on PDAs are numerous and include general drug references, specialized drug references (e.g., pediatrics, geriatrics, cardiology, infectious disease), diagnostic guides, medical calculators, herbal medication references, nursing references, toxicology references, and patient tracking databases. Costs and memory requirements for these programs can vary; consequently, the healthcare provider must limit the medication applications that are placed on the handheld computer.CONCLUSIONS:This article attempts to system...
The Blind Spot in the Patient Protection and Affordable Care Act's Cost-Control Policies

Provisions of the Affordable Care Act (ACA) help to reign in overuse within Medicare and the private markets. The author argues that the ACA is relatively silent on price control in the private mar...
Litigation Finance Ethics: Paying Interest

Over the last two decades, a shift in legal ethics has given rise to an expanding industry that specializes in lending money for the purpose of financing litigation. Plaintiffs and their attorneys now have a number of possible financing options that can provide the resources necessary to pursue their claims more fully. However, financing comes at a cost, and the question of who pays the cost implicates several ethical issues for attorneys. This article analyzes the propriety of attorneys borrowing funds for financing litigation and passing the funding expenses – origination costs and loan interest – through to their clients. It begins by tracing the evolution of the relevant legal ethics rules over the past century and reviewing the requirements that jurisdictions have imposed on attorneys seeking to pass litigation finance costs through, continues with an analysis of the leading case on point, and concludes with a review of a recent case that illustrates the obstacles that attorneys can encounter when seeking to pass litigation financing costs through to clients.
An Application of Equilibrium Size of Plant Analysis to Fluid Milk Processing and Distribution

This article reports the results of an empirical study in which a model for equilibrium size of marketing firm in a spatial market is used. This model has received extensive treatment in this JOURNAL, particularly from a theoretical standpoint. The model is applied to the processing and distribution of packaged fluid milk. Solution of the model results in determination of size of plant associated with minimum average processing and distribution costs. Results of the study indicated that where packaged milk is distributed in semitrailers, in most situations increases in distribution cost as plant size is expanded do not offset decreases in processing cost up to the 134,000 quart per day plant. While total average cost declines within this range of plant sizes, most of the economies of size are realized by the 50,000 quart per day level.
Longitudinally-Variable Hybrid Rocket Regression Rate Model with Radiation and Boundary Layer Effects

A hybrid rocket regression rate model is developed. This regression rate builds upon previous work to include the e ects of longitudinally variable mass ux, fuel surface temperature, radiant heat transfer, the ame temperature and ame height, and variation of properties in the boundary layer. A blowing parameter model based upon extrapolation of transpiration cooling data using the molecular weight of the pyrolysis products is described. An iterative solution process for this model is created and the resulting regression rate predictions are compared to experimental data from the literature as well as data collected from hybrid motor static tests at Utah State University. The higher delity regression rate model shows closer agreement with the experimental data than the prior regression rate model and also substantially reduces data scatter. Suggestions for further development are discussed.
Modeling and analysis of the upward burning of PMMA

Recent experiments in upward burning flame spread over solid materials have shown the importance of lateral entrainment in the dynamics of the flame evolution. The traditional 2-D solution proposed by ~mmons(1956)~ with extensions by Kodson, Williams and Buman (1968); Pagni and Shih (1976); and Annamalai and Sibulkin (1974); does not take lateral entrainment into account. For this reason, empirically determined B numbers from experimental measurements do not yield consistent values when plotted as a function of distance normalized by the pyrolysis length. A numerical model and experiments over PMMA are used to evaluate the main assumptions used in the Emmons solution. Flow characteristics (2-D Boundary Layer) and surface thermal balance are identified as the critical assumptions to be evaluated. Comparison of experiments, numerical results and the theoretical model serve to validate the assumptions leading to the definition of a mass transfer number but establish the need to model all three-dimensional features of the flow. B = C, = u g = Gr , = J Lv = Pr = Q = Qp = GI' = .,I qs,r 4; = Re = T = TiE, = Nomenclature
Intracellular movement of triacylglycerols in the intestine

The intestine can vary its triacylglycerol output rate depending on differing physiological conditions. The rate-limiting step in the complex process from fatty acid and monoacylglycerol entry to triacylglycerol export is un- known but suggested to be the transport of triacylglycerol from the endoplasmic reticulum to the Golgi. The present studies were carried out to test this hypothesis. The conver- sion rate of absorbed fatty acid to mucosal triacylglycerol was studied in rats infused intraduodenally with trioleoyl- glycerol, 135 m mol/h, for 6 h followed by ( 3 H)oleate. In 30 sec, 79% of the mucosal 3 H-labeled fatty acid was esterified to ( 3 H)triacylglycerol. The increase in the 3 H specific activ- ity of triacylglycerol in the endoplasmic reticulum and Golgi was studied in similarly prepared rats except that the radio- label was ( 3 H)trioleoylglycerol. The endoplasmic reticulum triacylglycerol specific activity was always less than that of the Golgi with a steady state not reached until 60 min of ( 3 H)trioleoylglycerol infusion. The steady state of ( 3 H)tria- cylglycerol in the lymph was not reached until 70 min of in- fusion. We conclude that the data are consistent with the rate-limiting step in intestinal triacylglycerol export being the movement of triacylglycerol from the endoplasmic retic- ulum to the Golgi as the conversion of absorbed fatty acid to triacylglycerol is rapid and the movement of triacylglyc- erol from the Golgi to the lymph is rapid as well.— Mans- bach II, C. M., and P. Nevin. Intracellular movement of tria- cylglycerols in the intestine. J. Lipid Res. 1998. 39: 963-968.
ANAYSIS OF EXPLORATION COST CHANGE IN OIFIELDS

The main items constituted of integrated cost are figured out by means of the analysis of internal structure of exploration cost in oilfields, and the present situation of integrated cost is reflected from the viewpoint of static; and the integrated cost summation and the change of unit cost can be identified by calculating the total cost of report time and basic time, ratio, unit cost and the rate of increasing and decreasing. Combining dynamics with static, the present situation and the change of the integrated cost can be fully analyzed. On the basis of studying on the static structure and dynamic increasing and decreasing rate o the integrated cost, the influence of cost changes of items on the changed of integrated unit cost is also analyzed to determine the main factors affecting the changes of integrated unit cost, which is he key in controlling the cost.
Attribute Reduction of VPRS and Determination of Its Parameter β Range

A new method was proposed to find a minimal reduction,which was based on VPRS(variable precision rough set) theory and broken the limitation of heuristic algorithm.Both the attribute reductions in VPRS and the range of their parameter β were considered in the new method and the reduction with the minimal number of attributes and the maximal range of β were selected as a minimal reduction.Corresponding algorithms to get all reduction and paramcter β were given and realized by MATLAB.The results show that these algorithms are more effective for the information system of less condition attributes.At last,an example was given to explain the validity and feasibility of algorithms.
Long-Term Effects of Prepubertal Testicular Vessel Ligation on Testicular Function in the Rat

AbstractTo determine the effects of unilateral testicular vein and artery ligation in the immature rat on the function and final location of the testis at adulthood, 10-day-old male rats underwent either a sham opearation or unilateral ligation of these vessels of the still undescended testis. Testicular location, blood flow, size and histology as well as ventral prostate weights were measured 50 days later at adulthood. At age 60 days, it was determined that all testes were descended into the scrotum, and there were no differences in testis and ventral prostate weights, intratesticular sperm counts and mean seminiferous tubular area between the control and sham operated animals. However, there was an 18% reduction in testicular blood flow (ml. per 100gm. per minute ± standard error of mean) in the operated animals when compared to the sham (20.43 ± 1.10 versus 16.69 ± 0.74, p <0.02).These data indicate that although there is a slight but significant reduction in testicular blood flow at adulthood when th...
Towards sedentary lifestyle prevention: An autoregressive model for predicting sedentary behaviors

Sedentary lifestyles are ubiquitous in modern societies. Watching television, playing video games, and using the computer while sitting are examples of sedentary behaviors that are now common worldwide. Multiple research studies have found that the length of sedentary time is linked with an increased risk of obesity, diabetes, cardiovascular disease, and all-cause mortality. Medical researchers have identified time, daily rhythm, and past sedentary habits as three determinants (causes) of sedentary behaviors. Building on these insights, in this paper we propose an approach to automatically discover patients' temporal patterns of sedentary behaviors from raw activity logs by using an autoregressive model with maximum entropy method. With this approach, health care providers will be able to predict patients' deleterious sedentary behaviors as evidence to drive computer-generated preventive interventions based on behavior change theories such as the Theory of Planned Behavior.