bluuebunny/crossref_metadata_2025 huggingface dataset:
Suppression of Pool Fire in a Large Enclosure with Water Mist
Authors: Lal Suresh , Gupta Meenakshi , Kushari A. , Kapoor J.C. , Maji S.
Published: September 2013

This paper reports the results of an experimental study of suppression of pool fires in enclosed spaces using water mist. The main objective of the present study is to understand the mechanisms responsible for the suppression of pool fires using water mists. Experiments were conducted in a large compartment with n-heptane pool fires of different heat release rates. The temperature variations in the compartment were measured using K-type thermocouples fixed at two locations. A multi gas analyzer was used to measure gas concentrations. The test results indicate that the water mist suppresses the diffusion flame in an enclosed space mainly through evaporating cooling and oxygen displacement by water vapors, resulting in inefficient combustion. The fire suppression time decreases with a decrease in droplet diameter. It is much easier to suppress a larger fire due to faster rates of evaporation of water droplets and therefore, the total mist requirement decreases with an increase in the fire size. The results of this study can find application in the design of water mist based fire fighting systems for indoor fires.
Analysis and Control of an Unstable Mode in a Combustor with Tuneable End Condition
Authors: Heckl Maria , Kosztin Béla
Published: September 2013

A major problem in the development of low-pollution combustion systems are thermo-acoustic instabilities, i.e. large-amplitude oscillations generated by a feedback between the unsteady heat release and acoustic waves. In order to develop robust control strategies, it is necessary to have a predictive model that captures the physics of the phenomenon. The aim of this paper is to present such a model for a dump combustor with a generic heat release law, and fitted at the inlet end with a perforated plate backed by a tuneable cavity. Our model leads to a simple governing equation for one acoustic mode in the combustor, and from this equation stability predictions can be made with a minimum of numerical effort. We will use it to examine the effect of various system parameters.
Inadequate Investment Impacting India's Innovation Returns - A Perspective
Authors: Banerjee Kaushik , Thakurta Rahul
Published: September 2013

Continuous innovation is critical for the sustainability and development of any society. Innovations should be focused not only at solving the existing needs of the society, but should be geared to the future. Innovation creates new industries, which creates new jobs and new markets while expanding existing ones — all of which contributes to the development of the society. The Indian economy is at a crossroads today, with a burgeoning middle class whose affluence and access to information has increased its appetite for innovative products and processes while still there is a huge population base that does not have access to even the minimum technological advances of the 21st century. India lacks in creating genuinely innovative products and processes/technologies that are new to the world. One of the primary reasons for this is the lack of technological competence in most Indian firms. However, it is wrong to say that there is a lack of innovation in India. The article identifies certain types of innovations in which India has become a leader, and the importance of such innovations in the Indian socio-economic context. It also identifies the limitations of such innovations and why such innovations, though important, may not be sufficient to either bridge the technology gap or generate enough value that can transform the technology landscape in India. It also identifies the limitations of wholesale importation of technologies in order to bridge the gap. To conclude, the authors provide some directions so that India can improve its technological competence as a first step towards developing innovative products and technologies.
The co-chaperones Fkbp4/5 control Argonaute2 expression and facilitate RISC assembly
Authors: Martinez Natalia J. , Chang Hao-Ming , Borrajo Jacob de Riba , Gregory Richard I.
Published: September 2013

Argonaute2 (Ago2) protein and associated microRNAs (miRNAs) or small interfering RNAs (siRNAs) form the RNA-induced silencing complex (RISC) for target messenger RNA cleavage and post-transcriptional gene silencing. Although Ago2 is essential for RISC activity, the mechanism of RISC assembly is not well understood, and factors controlling Ago2 protein expression are largely unknown. A role for the Hsc70/Hsp90 chaperone complex in loading small RNA duplexes into the RISC has been demonstrated in cell extracts, and unloaded Ago2 is unstable and degraded by the lysosome in mammalian cells. Here we identify the co-chaperones Fkbp4 and Fkbp5 as Ago2-associated proteins in mouse embryonic stem cells. Pharmacological inhibition of this interaction using FK506 or siRNA-mediated Fkbp4/5 depletion leads to decreased Ago2 protein levels. We find FK506 treatment inhibits, whereas Fkbp4/5 overexpression promotes, miRNA-mediated stabilization of Ago2 expression. Simultaneous treatment with a lysosome inhibitor revealed the accumulation of unloaded Ago2 complexes in FK506-treated cells. We find that, consistent with unloaded miRNAs being unstable, FK506 treatment also affects miRNA abundance, particularly nascent miRNAs. Our results support a role for Fkbp4/5 in RISC assembly.
On the proof-theory of a first-order extension of GL
Authors: Schwartz Yehuda , Tourlakis George
Published: September 2013

We introduce a first order extension of GL, called ML3, and develop its proof theory via a proxy cut-free sequent calculus GLTS. We prove the highly nontrivial result that cut is a derived rule in GLTS, a result that is unavailable in other known first-order extensions of GL. This leads to proofs of weak reflection and the related conservation result for ML3, as well as proofs for Craig’s interpolation theorem for GLTS. Turning to semantics we prove that ML3 is sound with respect to arithmetical interpretations and that it is also sound and complete with respect to converse well-founded and transitive finite Kripke models. This leads us to expect that a Solovay-like proof of arithmetical completeness of ML3 is possible.
The Modern Science of Multicriteria Decision Making and Its Practical Applications: The AHP/ANP Approach
Authors: Saaty Thomas L.
Published: September 2013

This paper presents a summary of the discrete mathematical part of my work, the Analytic Hierarchy Process (AHP) and its generalization to dependence and feedback, the Analytic Network Process (ANP), for measuring tangible and intangible factors, particularly as applied to decision making. The factors of the decision are arranged in hierarchical or network structures and judgments are then made by the decision maker, or by an expert, about the dominant element for each pair with respect to a common property. From simple judgments on two elements at a time with respect to a common property, priority vectors are obtained that are combined throughout the structure to give the best outcome for a decision. The judgments may be inconsistent, and there is a mathematical way to measure inconsistency so that the outlying judgments may be revised by the decision maker in an acceptable way or a decision may be delayed until more consistent information is obtained. In practical applications using either hierarchical or network structures, decisions are often analyzed in separate parts for their benefits, opportunities, costs, and risks, and the results are then combined in an appropriate way into an overall synthesis of those priorities. The mathematics has been generalized in the literature to the Neural Network Process (NNP), the continuous case for modeling how the brain synthesizes signals. There has been a diversity of applications over the past 30 to 40 years, and some of these are reported here. A brief mention is made of other methods of decision making and how AHP/ANP may compare with them.
The effect of surgical approach on the histology of the femoral head following resurfacing of the hip
Authors: Amarasekera H. W. , Campbell P. C. , Parsons N. , Achten J. , Masters J. , Griffin D. R. , Costa M. L.
Published: September 2013

Objectives

We aimed to determine the effect of surgical approach on the histology of the femoral head following resurfacing of the hip.

Methods

We performed a histological assessment of the bone under the femoral component taken from retrieval specimens of patients having revision surgery following resurfacing of the hip. We compared the number of empty lacunae in specimens from patients who had originally had a posterior surgical approach with the number in patients having alternative surgical approaches.

Results

We found a statistically significant increase in the percentage of empty lacunae in retrieval specimens from patients who had the posterior approach compared with other surgical approaches (p < 0.001).

Conclusions

This indicates that the vascular compromise that occurs during the posterior surgical approach does have long-term effects on the bone of the femoral head, even if it does not cause overt avascular necrosis. Cite this article: Bone Joint Res 2013;2:200–5.
Adsorption of radiocesium from aqueous solution using chemically modified pine cone powder
Authors: Naidoo Eliazer Bobby , Pholosi Agnes , Ofomaja Augustine Enakpodia
Published: September 2013

In this study, toluene–ethanol mixtures were investigated as chemical modifying agents for pine cone powder (PCP) and the optimum modification ratio determined by measuring the improvement in surface properties of the PCP such as Brunauer–Emmett–Teller (BET) surface area, bulk density, and surface negative charge. The modified adsorbents were then applied for the removal of cesium ions from aqueous solution. The result revealed that the chemically modified PCP had better surface properties than the raw BET surface area, and X-ray diffraction (XRD) spectra revealed that the surface area improved and cellulose crystallinity reduced. Cesium adsorption by the chemically modified PCP was much higher than for the raw PCP. Desorption studies were also performed to evaluate the mechanism of adsorption.
An Unconfined Swelling Test for Clayey Soils That Incorporates Digital Image Correlation
Authors: Lim B. F. , Siemens G. A.
Published: September 2013

A new laboratory test apparatus and methodology have been developed for characterizing the swelling potential of expansive soil under free stress conditions. Soil specimens are given access to water under true free swell conditions, and the maximum swelling potential is determined experimentally. Real-time deformation measurements and interpretation are obtained through digital image correlation using GeoPIV. The capabilities of the new test are illustrated using a remolded natural swelling soil. Both primary and secondary swelling behavior were observed during testing. The effect of the aspect ratio was assessed, and it was found that smaller specimens achieved equivalent swelling strains with significantly shorter test durations. The non-contact deformation results agree with the end-of-test hand measurements. The non-contact method also provides additional valuable information regarding the time-dependent swell behavior and evaluation of the end-of-test criterion. The results are interpreted using the Swell Equilibrium Limit, which is a unifying framework for the analysis and prediction of swelling soil deformations under defined initial and boundary conditions.
A New Method to Simulate Stress–Strain Relations from Multiple-Step Loading Triaxial Compression Test Results
Authors: Taheri A. , Tatsuoka F.
Published: September 2013

Multiple-step loading (ML) on a single specimen can be used to determine the peak compressive strengths at different confining pressures (σ′hS) of cement-mixed gravel (CMG) very similar to those obtained by single-step loading (SL) drained triaxial compression (TC) tests. However, only the unload/reload stress–strain relations at different σ′hS (except for the primary loading one at the first step) can be obtained from a ML test and the reloading relations become softer with an increase in the negative irreversible axial strain increment that has taken place during respective immediately preceding unloading regimes. This effect gradually decreased during reloading while it totally disappeared once large-scale yielding started. An empirical equation was developed to derive undamaged reloading stress–strain curves (URCs) by removing the damage effects from ML TC test measured reloading curves (MRCs). A new simple method was developed in the framework of proportional rule to simulate primary loading curves (PLCs) at different σ′hS from the MRCs from a given ML TC test using a correlation factor. A practical procedure for simulation of PLCs in a ML test were established and applied to generate PLCs in a ML test increasing σ′h and a ML test decreasing σ′h. The method was validated by comparing the PLCs simulated from the results of a pair of ML tests increasing and decreasing σ′h with those measured in a set of SL TC tests at different σ′hS.
cAMP in the pituitary: an old messenger for multiple signals
Authors: Peverelli Erika , Mantovani Giovanna , Lania Andrea G , Spada Anna
Published: September 2013

The cyclic nucleotide cAMP is a universal regulator of a variety of cell functions in response to activated G-protein coupled receptors. In particular, cAMP exerts positive or negative effects on cell proliferation in different cell types. As demonstrated by several in vitro studies, in somatotrophs and in other endocrine cells, cAMP is a mitogenic factor. In agreement with this notion, it has been found that the mutations of genes coding for proteins that contribute to increases in the cAMP signaling cascade may cause endocrine tumor development. This review will discuss the central role of cAMP signaling in the pituitary, focusing on the cAMP pathway alterations involved in pituitary tumorigenesis, as well as on poorly investigated the aspects of cAMP cascade, such as crosstalk with the ERK signaling pathway and new cAMP effectors.
Evolution After Whole-Genome Duplication: A Network Perspective
Authors: Zhu Yun , Lin Zhenguo , Nakhleh Luay
Published: September 2013

Gene duplication plays an important role in the evolution of genomes and interactomes. Elucidating how evolution after gene duplication interplays at the sequence and network level is of great interest. In this work, we analyze a data set of gene pairs that arose through whole-genome duplication (WGD) in yeast. All these pairs have the same duplication time, making them ideal for evolutionary investigation. We investigated the interplay between evolution after WGD at the sequence and network levels and correlated these two levels of divergence with gene expression and fitness data. We find that molecular interactions involving WGD genes evolve at rates that are three orders of magnitude slower than the rates of evolution of the corresponding sequences. Furthermore, we find that divergence of WGD pairs correlates strongly with gene expression and fitness data. Because of the role of gene duplication in determining redundancy in biological systems and particularly at the network level, we investigated the role of interaction networks in elucidating the evolutionary fate of duplicated genes. We find that gene neighborhoods in interaction networks provide a mechanism for inferring these fates, and we developed an algorithm for achieving this task. Further epistasis analysis of WGD pairs categorized by their inferred evolutionary fates demonstrated the utility of these techniques. Finally, we find that WGD pairs and other pairs of paralogous genes of small-scale duplication origin share similar properties, giving good support for generalizing our results from WGD pairs to evolution after gene duplication in general.
Structure and activity of the geothermal field of Hvalfjörður (Iceland) from brittle tectonic, geothermal and paleostress analysis
Authors: Bergerat Françoise , Sæmundsson Kristjan , Fourel Loïc , Angelier Jacques
Published: September 2013

This paper presents the results of brittle tectonic, palaeostress inversion, and hydrothermal mineralisation studies of the Hvalfjörður low-temperature geothermal field in Southwest Iceland. This geothermal field (including two pronounced thermal anomalies) is located in the highly altered core area of an extinct and deeply eroded Tertiary central volcano. Most of the geothermal water appears to be conducted by vertical extension fractures. Palaeostress analysis indicates a rather complex stress history, with four major trends of extension involving normal and strike-slip faulting modes as well as dyke injection. Analysis of the data on the relative chronology indicates that these four regimes were closely intricate in time and space. The most important regime is a NW-SE, rift-perpendicular extension related to the oceanic rifting in Iceland. This trend partly controls the past (Pliocene-Early Pleistocene) hydrothermal activity in the Hvalfjörður area; however, an E-W rift-oblique extension also occurred with a N-S trending fracture system including normal faults, dykes and veins that show higher levels of hydrothermal mineralisation. Currently, there is strong hot-water convection, producing a thermal anomaly, in this N-S-trending fracture system. Our study highlights the paleostress evolution and the development of fracture systems in Hvalfjörður, including the past geothermal history; nevertheless the most efficient tool in geothermal prospection in such complex area remains the shallow geothermal survey. It has proved successful in many localities in Early Pleistocene to Miocene rocks where no surface indication of geothermal activity exists.
Fracture patterns and their relations to mountain building in a fold-thrust belt: A case study in NW Taiwan
Authors: Chu Hao-Tsu , Lee Jian-Cheng , Bergerat Françoise , Hu Jyr-Ching , Liang Shen-Hsiung , Lu Chia-Yu , Lee Teh-Quei
Published: September 2013

The main purpose of this study is to analyse striated micro-faults and other types of fractures (including tensile and shear joints, and veins), in order to elucidate their relationships with regional folds and thrusts and regional tectonic stress. We take the fold-thrust belt (i.e., the foothills and the Hsuehshan range) in NW Taiwan as a case study, which is a product of the Plio-Pleistocene arc-continent collision. A total of about 760 and 1700 faults and other fractures, respectively, were collected at 41 sites in the field. We have identified four sets of bed-perpendicular joints in the study area. The observation of joints and bedding at each site indicates that most of the penetrative joint sets developed in the earlier tectonic stage of the pre-folding/pre-tilting event, illustrating the fact that the intersection of joint sets lies along the line perpendicular to the bedding plane. We thus interpret these sets as tectonic fractures under deep-seated tectonic stress. We used the regional fold axes as reference to define the four fracture sets. However, we found that complexity in the study area makes this rather tentative. Principal stress axes σ1, σ2, σ3, were calculated by means of inversion of fault slip data at each site. The ratio Φ that defines the shape of stress ellipsoid is generally small, indicating that the value of the maximum principal stress axe σ1 is much larger compared to that of σ2 and σ3, which are approximately equal. The paleostress regime was characterized by a combination of thrust and strike-slip tectonic regimes. Based on their geometric relationships with tilted bedding, we found most of striated micro-faults were strongly related to the regional folding and can be categorized as early-, during, and late-folding stages. We characterized two major directions for the compressive event, oriented N110–120°E and N150–160°E respectively, which provide additional evidence to delineate the debates about paleostress changes in the Taiwan mountain building process.
Late Jurassic-Early Cretaceous faulting in the Southeastern French basin: does it reflect a tectonic reorganization?
Authors: Homberg Catherine , Schnyder Johann , Benzaggagh Mohamed
Published: September 2013

We present new data constraining the Late Jurassic to Early Cretaceous evolution of the Southeastern French basin (SFB). Meso-scale faults with displacement of several decimeters to 1–2 meters were sampled for geometric and kinematic data analysis and the faulted and un-faulted sedimentary units were examined for sedimentologic and bio-stratigraphic purposes. Small-scale faults were also extensively collected to determine the local stress states during this period. Meso-scale normal faults formed during sediment deposition or before its complete lithification attest of a recurrent activity in the Late Jurassic to Early Cretaceous period in an overall extensional context. The fault network cutting the Oxfordian to Aptian sequences included normal faults of various trends, ranging between WSW-ENE and NNW-SSE. We show that the deformation mechanism in the SFB drastically changed in the Jurassic-Cretaceous transition (latermost Tithonian?), with the direction of extension rotating from a WNW-ESE to a NNE-SSW direction. Lateral thickness variation of the sequences, redistribution of sediments, faulting at various scales concur that the Early Cretaceous period marks a tectono-stratigraphic reorganization of the basin. We suggest that it traduces the rifting and later opening of the North Atlantic (main branch and bay of Biscay branch).
A Cultural Lens to Understanding Daily Experiences with Type 2 Diabetes Self-Management among Clinic Patients in M'Bour, Senegal
Authors: BeLue Rhonda , Diaw Mor , Ndao Fatou , Okoror Titilayo , Degboe Arnold , Abiero Beatrice
Published: September 2013

Diabetes is a steadily increasing threat in Sub-Saharan Africa (SSA). Factors such as urbanization, obesity, physical inactivity, and inadequate access to healthcare are believed to contribute to the increasing burden of diabetes. Interventions that optimize diabetes self-management are critically important since obtaining diabetes medications is challenging due to cost constraints and availability. Culture is a significant factor in shaping health behaviors such as diabetes self-management, where individual health behaviors operate in confluence with family, community, and social structures. This study examined experiences with diabetes self-management among clinic patients residing in M'bour, Senegal, using the PEN3 model as a cultural framework. Results indicate that financial challenges related to accessing medical care and adhering to the prescribed diabetic diet were the main barriers to diabetes management. Family dynamics serve as both supportive and inhibiting forces that influence the aforementioned barriers.
Healthcare-Seeking Behavior among the Chakma Ethnic Group in Bangladesh: Can Accessibility and Cultural Beliefs Shape Healthcare Utilization?
Authors: Uddin Jalal , Hossin Muhammad Zakir , Mahbub Farzana , Hossain Muhammad Zakir
Published: September 2013

Existing studies lack qualitative information on the perceived reasons for ethnic minority groups' healthcare choices, attitudes toward healthcare services, and common practices based on traditional cultural belief systems in Bangladesh. This study noted the important influence of culture and beliefs with regard to availing healthcare services. Informal sector providers such as para-professionals and traditional healers take the lead in rendering physically, financially, and culturally accessible healthcare services in the context of under-utilization of public healthcare facilities. Salient factors determining the choice of therapy were the perceived causes of illness and physical and financial access to the health services. These drivers of health seeking behavior in an increasingly pluralistic healthcare system need to be taken into account to strengthen the current healthcare delivery system and to design specific health education and healthcare promotion programs for the poor, hard-to-reach, and under-served ethnic minority.
Onset and Progression of Diabetic Glomerulosclerosis: A Prospective Study Based on Serial Renal Biopsies
Authors: Takazakura Eisuke , Nakamoto Yasushi , Hayakawa Hiroyuki , Kawai Kohzo , Muramoto Shingo , Yoshida Kohjiro , Shimizu Masahiko , Shinoda Akira , Takeuchi Jugoro
Published: September 2013

Clinical factors related to the development and progression of renal lesions were studied in twenty-three diabetics by the use of serial renal biopsies or autopsy. The results were as follows:

Most of the juvenile and intermediate type diabetics were poorly controlled, with the glomerular lesion progressing rather rapidly. In contrast, many cases of the adult type were able to be maintained under good control and the renal lesion neither developed nor progressed. Two of the adult type diabetics with poor control showed slowly and slightly progressing renal lesions.

The progression of glomerular lesions was significantly related to the control of blood glucose, type of diabetes, age at onset, type of treatment, and degree of obesity, but not to the duration of diabetes or the length of the follow-up period. There was a significant correlation between the type of diabetes and the control of blood glucose over the years.

Arteriolar lesions developed concurrently with the progression of the glomerular lesion. Retinopathy also had a tendency to develop in proportion to the progress of glomerular lesions although it was not statistically significant.

We have discussed the clinical factors responsible for the progression of diabetic glomerulosclerosis and have suggested that the type of diabetes rather than the degree of control of blood glucose might be more important in determining the development and progression of diabetic glomerulosclerosis. Nevertheless, the possibility remains that successful control of blood glucose may prevent or retard the development of diabetic glomerulosclerosis.
A Difference Between the Inheritance of Classical Juvenile-onset and Maturity-onset Type Diabetes of Young People
Authors: Tattersall Robert B , Fajans Stefan S , Arbor Ann
Published: September 2013

A difference in the inheritance of diabetes has been shown between the families of twenty-six patients with maturity-onset type diabetes of young people (MODY) and families of thirty-five patients with classical juvenile-onset diabetes (JOD).

In the families of MODY: 1) twenty-two of twenty-six (85 per cent) propositi had a diabetic parent; 2) 46 per cent of families showed direct vertical transmission of diabetes through three generations; 3) of forty-seven tested siblings twenty-five (53 per cent) had latent diabetes; 4) the diabetic phenotype in the families was consistent, most affected individuals having a noninsulin requiring type of disease. These findings are compatible with autosomal dominant inheritance of MODY, although they do not exclude multifactorial inheritance. In contrast, in the families of JOD: 1) only four (11 per cent) of propositi had a diabetic parent; 2) three generation inheritance was found in only two (6 per cent) of JOD families, and 3) of seventyfour tested siblings eight (11 per cent) were diabetic. This difference provides further evidence of genetic heterogeneity in diabetes mellitus and indicates that there is a need for careful definition of the phenotype of diabetes in populations in which the genetics of diabetes is to be analyzed.
Evaluation of the Three-hour Oral Glucose Tolerance Test in Detection of Significant Hyperglycemia and Hypoglycemia in Pregnancy
Authors: Abell D A , Beischer N A
Published: September 2013

Analysis of 2,000 consecutive patients who had a three-hour 50-gm. oral glucose tolerance test done in the third trimester of pregnancy has shown that the three-hour reading was not necessary for the diagnosis of gestational diabetes.

It was found that hyperglycemia and hypoglycemia (95th and 5th percentiles, respectively, for plasma glucose levels) were significantly associated with an increased risk for perinatal mortality. Furthermore, hyperglycemia was associated with an increased incidence of large-for-dates placentas and hypoglycemia with small-for-dates infants and small-for-dates placentas. These associations with hypoglycemia were seen to be greatest when this occurred at the three-hour level, and it was concluded that the three-hour measurement should be retained until the clinical significance of hypoglycemia in pregnancy is fully determined.
Apparent Accelerated Aging of Human Collagen in Diabetes Mellitus
Authors: Hamlin Clive R , Kohn Robert R , Luschin Jean H
Published: September 2013

The chronologic ages of human subjects were determined experimentally by enzymatic digestion of tendon collagen samples. Determined age closely matched actual age for individuals dying with a variety of major diseases. Juvenile diabetics did not fit this pattern; their experimentally determined ages were significantly greater than their actual ages. This raises the possibility of relationships between diabetes mellitus, changes in connective tissue, and accelerated aging.
Ethanol-induced Alterations of Glucose Tolerance, Postglucose Hypoglycemia, and Insulin Secretion in Normal, Obese, and Diabetic Subjects
Authors: Nikkilä Esko A , Taskinen Marja-Riitta
Published: September 2013

Ethanol at an average blood concentration of 1 mg. per milliliter enhanced the immediate (first-phase) and prolonged (second-phase) insulin response to an intravenous glucose load in nonfasting normal human subjects. Simultaneously, the glucose disposal rate was increased and the postglucose hypoglycemia was accentuated, resulting in definite hypoglycemic symptoms in some individuals. Oral glucose tolerance was not changed by ethanol administration, but the thirty-minute blood glucose and plasma insulin values were increased, suggesting that alcohol might accelerate the absorption of glucose from the gut. Ethanol given orally during evening hours (1.5 gm. per kilogram) caused a nocturnal hyperinsulinemia and a decrease of blood glucose, but not an actual hypoglycemia. Oral glucose tolerance and plasma insulin response tested the next morning, when ethanol had disappeared from the blood, were not influenced by drinking the previous evening. The K-value of intravenous glucose was increased at this time, however. When alcohol was administered for one week at a dose corresponding to 25 per cent of daily calories and substituting for fat, both the oral and intravenous glucose tolerances were impaired in each subject but the insulin response remained unchaged.

In obese nondiabetic subjects, ethanol did not potentiate the early insulin response to intravenous glucose but it increased the second phase of insulin secretion in response to sustained hyperglycemia. In contrast to conditions in nonobese subjects, the glucose disposal rate was not incresed and postglucose hypoglycemia was not accentuated by ethanol in overweight subjects. In insulin-deficient diabetic patients the absent early insulin response could not be restored by ethanol, and the late component of insulin release was little increased by alcohol infusion. Ethanol did not improve the glucose utilization of diabetic patients.
Deterioration of the Microcirculation in Diabetes
Authors: McMillan Donald E
Published: September 2013

Studies of the microcirculation in diabetes in the last fifteen years have concentrated heavily on anatomic and biochemical abnormalities of the capillary basement membrane. Greater insights into basement membrane changes have eclipsed the previous picture of widespread progressive deterioration of the entire microcirculation. The history, variety of organ involvement, pattern of circulatory decline, and associated anatomic, physiologic, and biochemical findings are re-examined so that recently described potential mechanisms for the development of diabetic microangiopathy may be understood in a broader perspective. The possible contributions of seven categories of diabetic changes to damage of the microcirculation are outlined. The categories are: (1) altered basement membrane, (2) altered cellular function, (3) cell metabolic changes, (4) altered blood flow properties, (5) distrubed hemostasis, (6) altered oxygen transport, and (7) altered hormone production. The variety of clinical manifestations in long-standing diabetes related to microangiopathy appears to be due to a combination of a widely variable over-all rate of progression and a differing ability of body tissues and organs to accommodate to the sequential circulatory changes. The slow rate of deterioration in most diabetics suggests that several abnormalities must interact to produce the observed progression. A clear understanding of the interactions responsible for diabetic microangiopathy is becoming more important as new options in the management of diabetes become available.
Insulin Degradation by Isolated Fat Cells and their Subcellular Fractions
Authors: Hammond James M , Jarett Leonard
Published: September 2013

Isolated frt cells and purified subcellular fractions of fat cells have been shown to degrade insulin to biologically inactive trichloroacetic-acid-soluble fragments. Further study of this activity has revealed the following characteristics:

1. Most of the insulin-degrading enzymes are intracellular, inaccessible to insulin or trypsin when fat cells are intact. More that 90 per cent of the recovered activity is found in the high-speed supernatant (cytosol) when cell fractionation studies are performed.

2. The plasma membrane contains significant insulin-degradative capacity, as shown by tryptic digestion of intact cells and cell fractionation.

3. The pH optimum of the cell-membrane insulin-degrading site is more acid than that of the cytosol activity, but the tow enzyme systems are similar with regard to substrate specificity, response to metabolic inhibitors, and elution volume of degradation products on gel filtration.

4. The plasma-membrane-degrading activity differs from the specific insulin-binding site with regard to saturation kinetics, optimum temperature, substrate specificity, sensitivity to sulfhydryl-blocking agents, and trypsin snesitivity.
Diabetic Complications in a Patient with Coexisting Anterior Hypopituitarism
Authors: Greenwood R H , Ireland J T , Jones D H , Mahler R F
Published: September 2013

We present a patient who developed insulin-requiring diabetes several years after the onset of symptoms of anterior hypopituitarism. It is likely that the hypopituitarism protected him against the development of diabetic retinopathy and glomerular basement membrane thickening but not against neuropathy and atheroma. The significance of this in relation to the growth-hormone-microangiopathy hypothesis is discussed.
Short-Term Treatment of Alloxan-Diabetic Rats with Intrajejunal Administration of Water-in-Oil-in-Water Insulin Emulsions
Authors: Shichiri Motoaki , Kawamori Ryuzo , Yoshida Michio , Etani Nobuaki , Hoshi Mitsuru , Izumi Kanji , Shigeta Yukio , Abe Hiroshi , Osaka Kanji
Published: September 2013

Alloxan-diabetic rats with fasting blood glucose levels above 300 mg./100 ml. were treated with intrajejunal administration of water-in-oil-in-water (W/O/W) insulin emulsions via an indwelling catheter at a dose of either 25 or 50 U./100 gm. body weight, three times daily for five to fourteen days. The course of diabetes was followed by determinations of glucose levels in blood and urine.

During treatment a significant reduction in urinary glucose levels was observed in all rats studied. In two rats treated with 25 U./100 gm., fasting blood glucose levels did not change significantly. In four of five rats treated with 50 U./100 gm., W/O/W insulin emulsions significantly lessened hyperglycemia during treatment. Quantitative estimates suggested that the effectiveness of 50 U./100 gm. of intrajejunal W/O/W insulin emulsions was comparable to that after intramuscular regular insulin at doses between 1 and 2 U./100 gm.

These results would indicate that diabetes can be controlled by enteral administration of insulin preparations.
Glucose in a Saharan Nomad Population–the Broayas, from the Toubou Ethnic Group
Authors: De Hertogh R , Vanderheyden I , de Gasparo M
Published: September 2013

Oral plucose tolerance was studied in the Toubou Broayas living in northeaster Niger. Mean fasting plasma level of glucose was 64 ± 22 (S.D.) mg./100 ml. Two hours after oral administration of 100 gm. glucose, the level was 74 ± 26 mg./100 ml. Plasma insulin levels were, respectively, 18 ± 13 and 36 ± 24 μU./ml. There was no sex difference. Older subjects had higher glucose levels and heavier females had higher insulin levels two hours after glucose administration. In six subjects (4 per cent) the plasma glucose level exceeded either 110 or 130 mg./100 ml. in the fasting state or after glucose administration, respectively, without, however, exceeding 150 mg./100 ml. in any of them. The low prevalence of glucose intolerance in this population is discussed with regard to their nutritional conditions (80 per cent carbohydrates) and their physical activity (nomadism). The Broaya group, in whom obesity is unknown, appears to be well adapted to its extreme environment.
Transport of Peptide Hormones Across Isolated Rat Mesentery: Effect of Human Serum-Bound Insulin
Authors: Simon James D , Antoniades Harry N
Published: September 2013

The exchange of 125I-insulin, 125I-glucagon, 125I-proinsulin, 125I-growth hormone, 131I-albumin, 14C-inulin, and 14C-dextran across isolated rat mesentery was studied in a diffusion cell. The passage of immunoprecipitable porcine 125I-insulin (0.88 ng./ml.) was not affected by porcine proinsulin (145 ng./ml.), crystalline porcine insulin (17.4 ng./ml.), human growth hormone (87 ng./ml.), bovine serum albumin (4.5 mg./ml.), or normal guinea pig serum (840 μg. protein/ml.). However, the rate of insulin exchange was reduced by guinea pig anti-insulin antiserum and partially purified human serum-bound insulin (175 μg. protein/ml.). Bound insulin at the same concentration did not affect the exchange of 125I-glucagon, 125I-growth hormone, 14C-inulin, or 14C-dextran. Further purification of bound insulin by Sephadex G-100 chromatography yielded an approximately 45,000 molecular-weight fraction that at 5 μg. protein permilliliter allowed essentially no insulin transport. This same fraction of bound insulin significantly inhibited the disappearance of immunoprecipitable porcine 125I-insulin from the incubation medium of isolated rat hemidiaphragms. Theses studies suggest that the transport of insulin across biologic membranes, mesothelium, and possible endothelium is specifically inhibited by bound insulin, a circulating macromolecule that possesses insulin-like activity.
Insulin Sensitivity of the Large Human Adipocyte in Vitro
Authors: Davidson Mayer B
Published: September 2013

Adipose tissue from twelve normal-weight and ten obese subjects on weight-maintaining diets and nine obese subjects on hypocaloric diets was removed at surgery and incubated in vitro. Basal glucose oxidation correlated significantly (r = 0.68, p < 0.005) with fat-cell diameter in subjects on weight-maintaining diets. This relationship was significantly altered (p < 0.02) in subjects on calorie-restricted diets. In tissue from subjects on weight-maintaining diets, physiologic concentrations of insulin (25 μU./ml.) significantly increased glucose incorporation into carbon dioxide (p < 0.005) and glycogen (p < 0.001). Maximum insulin-stimulated glucose oxidation (increase over basal) was significantly enhanced (p < 0.05) in tissue from obese subjects, whereas insulin-mediated glucose incorporation into glycogen was similar in controls and obese subjects on weight-maintaining diets. Insulin-stimulated glucose oxidation was imparied in tissue from subjects on hypocaloric diets although fat-cell diameter was similar to those of obese subjects on weight-maintaining diets.

The effect of insulin on glucose incorporation into glycogen in isolated adipocytes was also studied. There was no correlation between insulin-stimulated glycogen synthesis and cell diameter. When cells from the same individual were separated into small and large adipocytes by differential flotation, the insulin effect was similar whether expressed as absolute or per cent increase over basal.

These results indicate that in vitro glucose oxidation by adipose tissue, in both the absence and the presence of insulin, is largely determined by dietary factors. This may also be true for insulin-stimulated glycogen synthesis. No evidence is provided for the concept that the enlarged human fat cell of obesity is insensitive to insulin in vitro.
Perspectives in Current Diabetes Research
Authors: Cahill George F
Published: September 2013

The Thirteenth Research Symposium, sponsored by the American Diabetes Association in cooperation with itsits Indiana Affiliate and the University of Indiana School of Medicine, attracted an all-time high attendance of 227 research scientists, clinicians, and academicians to the Eli Lilly Center in Indianapolis, October 16 and 17, 1975.

Co-directors of the Symposium were John A. Galloway, M.D., of the University of Indiana School of Medicine, Philip Felig, M.D., of Yale University School of Medicine, and Gerold M. Grodsky, Ph.D., of the University of California, San Francisco.
Basement Membrane Thickness in Muscle Capillaries of Normal and Spontaneously Diabetic Macaca Nigra
Authors: Howard Charles F
Published: September 2013

The thickness of the capillary basement membrane of femoral muscle was examined in normal and spontaneously diabetic Macaca nigra. Thickness correlated significantly with the degree and severity of diabetes; greater thickness was associated with decreased glucose tolerance, decreased serum insulin, and increased glucose and triglyceride. In normal monkeys, the average basement membrane thickness was 696 Å and in diabetic monkeys, 837 Å. The minimum basement membrane thickness was 524 Å in normal monkeys and 634 Å in diabetics. Normals differed significantly from diabetic monkeys.
Immunoperoxidase Demonstration of Human Serum Globulin Binding to Islet Tissue
Authors: Sorenson Robert L , Shank Richard D , Elde Robert P
Published: September 2013

Sera from juvenile diabetic and nondiabetic controls were tested, using the immunoperoxidase method, for the presence of isletbinding immunoglobulins. All diabetic sera tested contained an islet-binding protein and on the average the sera were more positive than age-matched controls. Normal adult sera are undifferentiated from juvenile diabetic sera. Most sera from children less than two years of age did not bind to islet tissue and sera from cystic fibrosis patients had a markedly diminished ability to bind to islet tissue. The binding protein appears to be an immunoglobulin which selectively reacts with elements of the islet beta cell.
Cell Membrane Changes in Chronically Diabetic Rats
Authors: Chandramouli V , Carter James R
Published: September 2013

We have examined the effect of chronic diabetes mellitus upon cell membrane composition and turnover in streptozotocin-treated rats and control animals maintained for four to eight weeks. Liver plasma membranes, prepared from diabetic animals, showed enhanced activities of alkaline phosphatase and glucose-6-phosphatase and depressed 5'-nucleotidase when compared with controls. Studies of the nonprotein constituents of liver plasma membranes and red cell “ghosts” showed similar changes in both tissues: sialic acid and cholesterol content were reduced in the membranes of diabetic animals, while phospholipids (total and individual classes) and neutral sugars were unchanged.

To look for changes in relative turnover rates of individual membrane proteins, we combined a double-label in-vivo technic using [3H] and [14C] leucine with polyacrylamide gel separation of membrane proteins. No significant differences were observed between control and diabetic animals.

In chronically diabetic animals, cell membranes may show significant changes in overall composition with no significant changes in the rate of protein turnover.
HL-A System and Diabetes Mellitus
Authors: Cudworth A G , Woodrow J C
Published: September 2013

HL-A antigens were determined in 100 patients with diabetes mellitus. When the data are combined with that from other studies, there is a definite positive association of acute-onset juvenile diabetes mellitus with HL-A8 and W15. Four families are described in which two or more members with this type of diabetes are present, and in each family, affected individuals share a haplotype including HL-A8 or W15. These findings are consistent with the possible role of immune response genes in the HL-A chromosomal region which might control the immune response to virus infections capable of producing islet cell damage.
Multiple Metabolic Functions of Glucose in Rat Pancreatic Islets
Authors: Pace Caroline S , Ellerman Jeanette , Hover Barbara A , Stillings Susan N , Matschinsky Franz M
Published: September 2013

Metabolic interactions between glucose and amino acids were studied with isolated rat islets using glucose utilization and lactate formation as indicators. Certain amino acids (8–10 mM) are capable of greatly stimulating lactate formation from 5 mM glucose. On a molar basis L-isoleucine is the most potent stimulator in a group of twenty-six amino acids. A physiological amino acid mixture (7.5–14 mM) or L-isoleucine (8 mM) profoundly altered the basic sigmoidal relation between glucose concentration in the medium and the rate of glucose utilization and lactate formation: with basal glucose (5 mM) both glucose utilization and lactate production were stimulated by the amino acid mixture and by L-isoleucine; at high glucose levels utilization was decreased by the amino acid mixture, but was unaffected by L-isoleucine, whereas lactate formation was decreased by both additions. The data indicate that amino acids may play a significant role in regulating the extent to which glucose serves as a fuel of pancreatic islet cells and in determining the pathways of glucose metabolism.

In order to elucidate the mechanisms of the amino acid effect, studies with phloridzin, ouabain, iodoacetate, cytochalasin B, and Na±deficiency were performed with the most effective amino acid, L-isoleucine. Each of these agents and Na±deficiency substantially reduced or completely blocked the extra lactate formation induced by L-isoleucine (8–10 mM). The intracellular uptake of 14C L-isoleucine by isolated islets was found to be Na±independent, and uphill transport of this amino acid was not detectable, whether basal glucose was present in the medium or not.

The action of iodoacetate in blocking glycolysis was reinvestigated. After forty-five minutes of exposure, 0.2 mM iodoacetate completely blocks lactate formation as well as glucose utilization. This confirms and extends earlier data from this laboratory and suggests that this SH-reagent indeed allows dissociation of the fuel and releasing functions of glucose.
Transplantation of the Islets of Langerhans and the Histocompatibility of Endocrine Tissue
Authors: Barker Clyde F
Published: September 2013

The passing of Dr. Arnold Lazarow on June 26 was a loss to the science of diabetology. Dr. Lazarow, Professor and Chairman of the Department of Anatomy, University of Minnesota School of Medicine, Minneapolis, was Codirector of the Twelfth Research Symposium of the American Diabetes Association and Chairman of one of the three sessions. As a tribute to him, the Association herewith presents a summary of the Symposium.