bluuebunny/crossref_metadata_2025 huggingface dataset:
Law, Religion, and the Present Danger
Authors: Berman Harold J.
Published: September 2018

When the word "law" is juxtaposed with the word "religion," an American lawyer today is apt to think immediately of the First Amendment to the United States Constitution with its double protection against any governmental interference in "the free exercise" of religion on the one hand and against any governmental "establishment" of religion on the other. From the standpoint of contemporary American constitutional law, religion has become the personal and private affair of individual citizens or groups of citizens. Indeed, in recent decades our courts, in interpreting the "free exercise" clause, have gone far toward immunizing individual and group activities from governmental control, whether federal or state, whenever they are considered by the persons engaging in them to be of a religious character; and at the same time, under the "establishment" clause the courts have struck down most forms even of indirect governmental support of religion, whether federal or state.
The Two White Races in South Africa
Authors: Mesenbring David
Published: September 2018

Most Americans concerned for South Africa tend to fault Afrikaans-speaking whites for apartheid and to look with hope toward the English-speakers. As a result, Afrikaners have tended to become isolated, easily written off as stubbornly intransigent in their racism. This habit of mind misrepresents the larger and more powerful group of whites who, given their Christian moralism, may be overlooked as a hidden resource for change. My experiences with a wide variety of South Africans provide reason to suggest a revisionist approach. Some historical background on the two white communities may help the reader to make sense of this suggestion.
I Want 'Rotten Bourgeois Democracy'!": An Interview With Rumanian Dissident Paul Goma
Authors: Jacqueney Theodore
Published: September 2018

GOMA: I think only about existing conditions, because under the existing circumstances thinking about a future ideal seems like thinking about a Utopian fantasy. I concentrate on thinking about improving the present condition of life in Rumania. If I were free to think about my ideal of government, it would be a "rotten bourgeois democracy." Make sure you put those last three words in quotation marks, because I am quoting the Rumanian Government's words.
Pinochet's Chile
Authors: Remmer Karen L.
Published: September 2018

In recent years no country in Latin America has played a more important role in raising questions about the goals and instruments of U.S. foreign policy than Chile. The revelations of U.S. involvement in the overthrow of the Allende government opened the door to far-reaching criticisms of the activities of U.S. intelligence agencies and helped generate the Carter administration's human rights policy. Today this policy is facing one of its sternest tests in Chile.
Hunger in China: The Failure of a System?
Authors: London Miriam , London Ivan D.
Published: September 2018

Why have many economists missed the fact of persistent malnutrition, hunger, and famine in the People's Republic of China? The fault is certainly not in their expertise (remarkably sophisticated in application, given the dubious nature of the data available) but in their interpretive comments and conclusions, which often seem gratuitous, deriving neither from estimates of per capita grain consumption nor from any visible basis in fact.
A Conversation With Andrew Young
Authors: Ogunlana Olujimi
Published: September 2018

Thus spoke America's U.N. ambassador, Andrew Young, during a press conference at the U.S. State Department after submitting his letter of resignation to President Carter on August 15, 1979. Young's resignation followed his "secret" meeting with the Palestine Liberation Organization's U.N. observer, Zahdi Labib Terzi, which violated U.S. policy of no contact with PLO representatives, a policy initiated in 1975 by former U.S. Secretary of State Henry Kissinger.
The Americans Are Coming!
Authors: Kirk Donald
Published: September 2018

The Americans are coming—not merely statesmen and diplomats, not just occasional journalists or teams of scholars or family planners or whatever, but almost anyone with enough money to pay for the privilege and accept some of the nuisance of guided tourism through the People's Republic of China. They jostle for space outside the panda pens of the Peking zoo, madly clicking cameras and shouting greetings at one another. They troop through the courts of the Forbidden City and the Summer Palace, mingling with grinning off-duty People's Liberation Army soldiers and hordes of uniformed schoolchildren. They crowd the orchestras of theatres and concert halls, applauding newly revived “revolutionary” operas and dances, often with more spontaneous verve than do the respectfully restrained Chinese around them.

The spectacle of Americans in garish, multicolored dress swirling through the lobbies of Peking's halfdozen hotels for foreigners provides a startling contrast to the normal sight of Ma9-suited Chinese bicycling methodically along broad avenues or crowding sidewalks through districts in which tourists until this year were distinct rareties. The Fifth National People's Congress was in full swing in early March when the first batches of American “friends” with no special professional or political affiliations began arriving. By the end of December some fifteen thousand of them had made the tour—a minuscule figure by the standards of virtually any other nation, but a great leap from the tojal of three thousand American visitors in 1977.
Civil Defense—the New Debate
Authors: Morgenthau Hans J.
Published: September 2018

It is impossible to state with assurance what the policy of the Carter administration is with regard to civil defense. As in so many other fields of policy, the policy of the Carter administration with regard to civil defense is contradictory in different respects. Successive statements of the same officials contradict each other. The statements of different officials contradict each other Official statements are contradicted by the actual policy pursued. The realities of the situation militate against the policy announced.

For the purpose of clarifying the issue let us assume that the administration is committed to a greatly expanded civil defense effort over several years, meaning primarily the evacuation of the bulk of the civilian population from the cities. Such a policy is, according to the New York Times, “farcical” on several grounds.
Civil Defense—the New Debate
Authors: Johnson David T.
Published: September 2018

While the Carter administration is clearly paying more attention to civil defense and will undoubtedly request more funding for crisisrelocation planning, this does not yet constitute giving "major priority" to civil defense. Most policymakers seem to believe civil defense can play only a very limited role in mitigating the effects of nuclear weapons.

Many of the questions related to the desirability or undesirability of more stress on civil defense are essentially unanswerable. We simply cannot know with assurance how it will affect U.S. security or the chances of nuclear war. Plausible points can be made on both sides, but it is mostly speculation. Nobody who feels strongly one way or the other is likely to have his views changed. The debate will be predictably inconclusive.
The U.N. and the (Economic) Education of Henry Kissinger
Authors: Stalson Helena
Published: September 2018

Something remarkable and of historic importance took place in New York during the first two weeks of September, 1975. At a Special Session of the United Nations the poor countries of the world, who have 70 per cent of its people and 30 per cent of its income, demanded that the rich, countries make some major changes in the international system. And the rich countries, including the United States, responded in new ways. Most reporters failed to notice how remarkable the events were, but the evidence is there.
Anti-Zionism=Anti-Semitism: Fact or Fable?
Authors: Pawlikowski John T.
Published: September 2018

On November 10 the United Nations General Assembly adopted a resolution defining Zionism as “a form of racism and racial discrimination.” The vote was 72-35 with 32 abstentions. A week earlier Abba Eban had written in the New York Times that “there is…no difference whatever between anti-Semitism and the denial of Israel's statehood. Classical anti-Semitism denies the equal rights of Jews as citizens within society. Anti-Zionism denies the equal rights of the Jewish people to its lawful sovereignty within the community of nations. The common principle in the two cases is discrimination.” Mr. Eban's words, coming as they did, not in the midst of a pro-Israel rally, but in a reflective column from a widely respected figure in the international community, a man who has not hesitated to criticize publicly aspects of his own government's policies toward the Arabs, must be accorded a special seriousness.
President Park and His Learned Friends
Authors: Kang Sugwon
Published: September 2018

In 1969. eight years after his armed usurpation. President Park Chung Hee of South Korea had his country's constitution amended so that he could seek a third term. Three years ago, in October, 1972. as he was serving his last term under the new rules. Park declared martial law, dissolved the National Assembly, and suspended the constitution. He did all this, as we were told then, in order to cope better with the “stark realities of a rapidly changing international situation.” Park was referring to East-West détente, which he viewed as a deadly threat to one of the twin pillars of his legitimacy; anticommunism and economic modernization.
Data Border Crossings
Authors: Roche Edward M. , Dell David J.
Published: September 2018

Most of us are well aware that the world is being changed by new information technologies, especially in the area of computers and telecommunications. Fewer are aware that these same technologies have stimulated major policy debates in international councils and within the economic and foreign policy-making chambers of an ever-increasing number of nations. Generally, these debates focus on the economic and political impact of technologies that enable computer data to be sent across national borders, a process known as transborder data flow (TDF). But transborder data flow has given rise to complex social and moral questions as well. At issue are such matters as national sovereignty and security, and the right of citizens to privacy and freedom of speech.
Anatomy of Resistance
Authors: Leiken Robert
Published: September 2018

In early March of last year I received an invitation to meet with the leaders of the Salvadoran guerrillas in Managua, Nicaragua. I was told that they had already translated and discussed the testimony on Central America I had prepared for a congressional subcommittee the previous September and had found it "educational." Now they wanted a "broad exchange of views" and also to transmit a "message" to the State Department before the Salvadoran elections scheduled for March 28.
Lobbying for Human Rights
Authors: Diuguid Lewis H.
Published: September 2018

The oppressed peoples of Latin America are abundantly represented these days in Washington. A human rights lobby, motivated by idealism of ideology rather than economic gain, carries an often eloquent approximation of the Latins’ case to Congress and the executive branch. These efforts are low-budget but high-key and, according to those being lobbied, can be every bit as influential as those of the sugar or arms interests.

Whether the lobby is truly effective at saving lives and protecting rights depends ultimately on whether the government it seeks to influence is effective at those tasks—and that remains an open issue in this contentious capital. The lobby, which already had established a rapport with sympathetic congressmen during Gerald Ford's presidency, now has at least as intimate a working relationship with the expanded human rights section of President Carter's State Department.
Small Lives for Big Words: Individualism and State Power Reconsidered
Authors: Horowitz Irving Louis
Published: September 2018

Once upon a time, earlier in the twentieth century, individualism was a doctrine that could be readily dismissed as archaic, idiosyncratic, and simply out of phase with the modern fashion. Even those who wanted to make a place for the individual were compelled to speak apologetically about the “new individualism” as a kind of hybrid of social welfare economy in contradistinction to the old individualism. Henry Steele Commager reminded us in 1950 that “the phenomenon of socialization was a logical expression of the American temperament in the new century. It reflected that decline of the importance of individualism and that growing awareness of social responsibility that could be noted similarly in law, education, business, and legislation.“
Human Rights for Tibetan Americans: No Small Questions
Authors: Akar Tinley Nyandak
Published: September 2018

A few months ago President Carter's human rights stature took a dive when the Department of State rejected the requests of a group of American citizens to have “Tibet,” instead of China, listed as their birthplace on their U.S. passports. The decision came on the heels of an announcement that Zbigniew Brzezinski would be visiting China a few weeks later.

Despite the president's repeated assertions about his impartial application of human rights to all nations, the administration has been silent when it comes to human rights violations by the People's Republic of China. Evidently Washington does not want to offend Peking and thus lets China dictate, at least indirectly, an internal policy decision of the United States. The action by the State Department regarding American citizens of Tibetan origin has carried this unequal application of human rights principles to an absurd degree.
Effects of frequency and morphosyntactic structure on error detection, correction, and repetition in Swedish-speaking children
Authors: HALLIN ANNA EVA , REUTERSKIÖLD CHRISTINA
Published: September 2018

Grammatical error detection and correction are often used to test explicit language knowledge. This study investigated effects of token frequency and error type in error detection, correction, and repetition, and performance on the three tasks were compared and related to models of metalinguistic awareness and development. Thirty Swedish-speaking 10-year-olds with typical language development participated in the study, which focused on four morphosyntactic errors: the infinitive instead of past tense for regular and irregular verbs, and the omission of the obligatory indefinite article in common and neuter gender noun phrases. Target verbs and nouns were of high or low frequency. Results showed significant effects of verb frequency in all tasks, and effects of noun gender for error detection, but not for correction and repetition. Children detected significantly more past-tense errors than they accurately corrected, but the opposite result was seen for noun phrase errors. The patterns of results both within and across tasks imply that implicit language knowledge affects performance, and that lexical frequency, even of familiar words, needs to be controlled when designing tasks for measuring grammatical knowledge. The particular challenge of the Swedish neuter noun phrase in language development and language processing needs to be further investigated.
A spatial analysis of land use and cover change and agricultural performance: evidence from northern Ghana
Authors: Haile Beliyou , Signorelli Sara , Azzarri Carlo , Guo Zhe
Published: September 2018

Using remotely sensed land-cover data in 1994 and 2014, and cross-sectional survey data in 2014, this study examines the association between land use and cover change and agricultural productivity in northern Ghana. We document a significant expansion of crop land and settlements (productive use) at the expense of natural vegetation cover. Land areas converted from natural cover to productive use have higher maize yield (0.17 tons per hectare) and harvest value (1,021 Ghanaian Cedi) compared with those converted from bare soil to productive cover. Moreover, areas that were covered by shrubs or savannah in 1994 were more productive in 2014 relative to bare soils in 1994. Although our data do not allow us to establish causality, the evidence suggests the importance of past land-cover conditions in affecting current agricultural performance, especially in resource-stricken settings where conservation and restoration practices are not as common.
The psychosocial issues of women with cancer of the vulva
Authors: Boden J. , Willis S.
Published: September 2018

Background

Cancer of the vulva is rare, it is a disease commonly diagnosed in elderly women, however, the incidence in younger women is rising. Many patients diagnosed and treated for vulval cancer face physical, social, sexual and psychological challenges. It is essential that therapy radiographers and members of the wider multidisciplinary team understand such challenges in order to provide patient centred care.

Aim

This review aims to highlight the key psycho-social issues experienced by patients with cancer of the vulva, identifying implications for practice in order to improve the holistic care for this patient group.

Method

A search of English literature was performed using Medline, Pubmed, CINAHL and PsycINFO. Search terms included, vulva or vulval cancer, psychosocial, psychosexual impact and quality of life. Articles were excluded if they focussed on cancers other than gynaecological and vulval cancers.

Results and Conclusions

Although there are numerous reports on the psychological and psychosocial problems faced by gynaecological cancer patients; there was a paucity of literature pertaining to patients with cancer of the vulva, this is consistent with previous research. Studies show a significant negative, psychosocial impact experienced by these women. Common themes being isolation, loneliness, stigmatisation and lack of information for patients and their carers, themes spanning over three decades. Nevertheless, it is important to be aware of the findings from recent studies consistent with patient’s needs, highlighting that listening to women’s narratives on living with cancer of the vulva is essential if we are to help with the psychosocial issues experienced by these women. They underline a necessity to raise awareness among healthcare professionals and the general public, to improve holistic support for this particular group of women. This is particularly important in the radiotherapy setting as many of these women undergo lengthy courses of treatment and the appropriately trained therapeutic radiographer can play a vital role in addressing the physical and psychosocial problems.
Two Synoptic Routes to Subtropical Heat Waves as Illustrated in the Brisbane Region of Australia
Authors: Quinting J. F. , Parker T. J. , Reeder M. J.
Published: September 2018

The physical mechanisms by which heat waves in the Brisbane region of Australia develop are elucidated through trajectory and composite analyses. Trajectories are started close to the surface during heat waves and integrated backward. Those trajectories for which the net diabatic heating lies in the uppermost pentile are called strongly diabatic, while those in the lowermost pentile are called weakly diabatic. In the weakly diabatic case, air parcels originate eastward of the continent over the ocean and warm almost entirely by adiabatic compression in an anticyclonic environment. Surprisingly, strongly diabatic heat waves in this region are characterized by an upper‐tropospheric cyclonic anomaly off the southeastern corner of Australia. The air parcels originate far to the southwest of the heat wave, and their temperature increases roughly in equal parts by adiabatic compression as air parcels subside on the rear flank of this cyclonic anomaly and surface sensible heating as air parcels are advected horizontally.
Wave Runup Over Steep Rocky Cliffs
Authors: Dodet G. , Leckler F. , Sous D. , Ardhuin F. , Filipot J.F. , Suanez S.
Published: September 2018

Wave runup is known to depend on offshore wave conditions and coastal morphology. While most field studies on wave runup have focused on low‐to‐mild‐sloping sandy beaches, runup measurements on steep and irregular rocky cliff profiles are still very scarce. Here we investigate the physical processes controlling wave runup in such environments and the range of applicability of empirical runup formula. This study focuses on the steep rocky cliffs (0.1 < tanβ < 0.4) of Banneg Island, a small island located in the Molène archipelago, Brittany, France, occasionally flooded during extreme water level events. A statistical parameter for extreme runup is derived from the measurements of pressure sensors deployed in the intertidal zone. Deep water wave parameters are used to force a high‐resolution wave model, and nearshore wave parameters and high‐resolution topographic data are analyzed concurrently with runup time series in order to assess the dependence of the runup on hydrodynamic conditions and morphological parameters. The wave runup is shown to be strongly related to the square root of the offshore significant wave height times the offshore wavelength. The measurements also reveal the depth dependence of the runup, which is mainly attributed to the curvature of the foreshore profile. In comparison to empirical relation obtained for a mild‐sloping beach, the present data show a significant reduction in normalized wave runup, that is attributed to enhanced bottom friction over the rocky bottom.
Snow Depth Retrieval on Arctic Sea Ice From Passive Microwave Radiometers—Improvements and Extensions to Multiyear Ice Using Lower Frequencies
Authors: Rostosky Philip , Spreen Gunnar , Farrell Sinead L. , Frost Torben , Heygster Georg , Melsheimer Christian
Published: September 2018

Snow on sea ice influences the Arctic energy and heat budgets and is therefore important for Arctic climate studies. Methods to derive snow depth based on satellite‐borne microwave radiometer observations have existed since the 1990s. However, in the Arctic the most widely used algorithm can only be applied over first‐year ice (FYI) and does not make use of the lower frequencies, which are available since 2002. Here we present three improvements to the current passive microwave snow depth retrieval: (a) We derive new coefficients based on a regression analysis using 5 years of Operation IceBridge airborne snow depth measurements. (b) We extend the algorithm to take advantage of the lower frequency channel at 7 GHz. (c) We consider an extension of the snow depth retrieval to multiyear ice (MYI) during spring. Our results show that the gradient ratio, GR(19/7) is most suited for deriving snow over both Arctic FYI (R =°−0.73) and MYI (R = −0.57). An evaluation of the new retrieval with Operation IceBridge snow depth measurements from March and April 2015 shows a good agreement over FYI (difference = −2.1 cm; 93% of the differences below 5 cm). Over MYI the difference is −4.0 cm and 56% of the differences are below 5 cm, that is, the root mean square distance (RMSD) is larger over MYI than over FYI. We demonstrate for the first time that spring snow depth measurements can be derived from passive microwave observations over both FYI and MYI.
A Direct Estimate of Volume, Heat, and Freshwater Exchange Across the Greenland‐Iceland‐Faroe‐Scotland Ridge
Authors: Rossby T. , Flagg C. , Chafik Leon , Harden Ben , Søiland Henrik
Published: September 2018

The flow of warm salty water toward the Nordic Seas is of fundamental importance to the climate of central and northern Europe. In an effort to gain an improved quantitative assessment of these fluxes a program was started in 2008 to measure upper‐ocean currents from the high‐seas ferry Norröna, which operates out of the Faroes to Iceland and Denmark. The current measurements were made with an acoustic Doppler current profiler mounted in the Norröna's hull. Starting in fall of 2013 monthly deployments of Expendable BathyThermographs give comprehensive information on the temperature field. These velocity and temperature data can be combined to estimate mean volume and temperature fluxes (referenced to 0 °C) for the two sections. Archived hydrographic data give us the corresponding salt transport. Thanks to an array of 12 tall moorings across the Blosseville Basin that measured currents, temperature, and salinity net transport of volume, temperature, and salt between Iceland and Greenland can also be estimated. By combining the velocity data from these three sections the strength of the Nordic Seas branch of the meridional overturning circulation is estimated to be 7.7 ± 0.8 Sv where 1 Sv = 106 m3/s. Imposing the constraint of zero net volume and salt flux, the corresponding heat and freshwater fluxes are estimated to be 264 ± 27 TW (1 TW = 1012 W) and −0.104 ± 0.01 Sv, respectively. The uncertainties in heat and freshwater fluxes are largely governed by volume fluxes. The Norröna program is ongoing.
Loss of mdig expression enhances DNA and histone methylation and metastasis of aggressive breast cancer
Authors: Thakur Chitra , Chen Bailing , Li Lingzhi , Zhang Qian , Yang Zeng-Quan , Chen Fei
Published: September 2018

We previously reported that expression of an environmentally induced gene, mineral dust-induced gene (mdig), predicts overall survival in breast cancer patients. In the present report, we further demonstrate the differential roles of mdig between earlier- and later-stage breast cancers. In noncancerous breast, mdig is a proliferation factor for cell growth and cell motility. In breast cancer, however, higher levels of mdig negatively regulate the migration and invasion of cancer cells. Assessment of global DNA methylation, chromatin accessibility and H3K9me3 heterochromatin signature suggests that silencing mdig enhances DNA and histone methylation. Through immunostaining and data mining, we found that mdig is significantly upregulated in noninvasive and/or earlier-stage breast cancers. In contrast, in triple-negative and other invasive breast cancers, diminished mdig expression was noted, indicating that the loss of mdig expression could be an important feature of aggressive breast cancers. Taken together, our data suggest that mdig is a new biomarker that likely promotes tumor growth in the early stages of breast cancer while acting as a tumor suppressor to inhibit invasion and metastasis in later-stage tumors.
Cryo-EM analysis of the T3S injectisome reveals the structure of the needle and open secretin
Authors: Hu J. , Worrall L. J. , Hong C. , Vuckovic M. , Atkinson C. E. , Caveney N. , Yu Z. , Strynadka N. C. J.
Published: September 2018

The bacterial type III secretion system, or injectisome, is a syringe shaped nanomachine essential for the virulence of many disease causing Gram-negative bacteria. At the core of the injectisome structure is the needle complex, a continuous channel formed by the highly oligomerized inner and outer membrane hollow rings and a polymerized helical needle filament which spans through and projects into the infected host cell. Here we present the near-atomic resolution structure of a needle complex from the prototypical Salmonella Typhimurium SPI-1 type III secretion system, with local masking protocols allowing for model building and refinement of the major membrane spanning components of the needle complex base in addition to an isolated needle filament. This work provides significant insight into injectisome structure and assembly and importantly captures the molecular basis for substrate induced gating in the giant outer membrane secretin portal family.
Human augmentation of ecosystems: objectives for food production and science by 2045
Authors: Funabashi Masatoshi
Published: September 2018

Current food production systems require fundamental reformation in the face of population growth, climate change, and degradation of health and the environment. Over the course of human history, every agricultural system that has emerged has featured some sort of trade-off between productivity and environmental load. These trade-offs are causing the planet to exceed the boundaries of its biogeochemical cycles and are triggering an unprecedented extinction rate of wild species, thus pushing global ecosystems to the brink of collapse. In this era, characterized as it is by human activity that can profoundly influence climate and the environment (i.e., the Anthropocene epoch), tipping points can be either negative or positive. While a negative tipping point can produce sudden, rapid, and irreversible deterioration of social and environmental systems, a positive tipping point can produce improved health and sustainable social-ecological systems. The key to promoting positive global tipping points is a thorough understanding of human activity and life history on an evolutionary scale, along with the comprehensive integration of science and technology to produce intelligent policies and practices of food production, particularly in the developing world (See Supplementary Material 1 summary for policymakers). Simply increasing the efficiency and scale of monoculture-intensive agriculture is unlikely to drive social-ecological change in a positive and sustainable direction. A new solution to the health-diet-environment trilemma must be developed to achieve a net positive impact on biodiversity through the anthropogenic augmentation of ecosystems based on the ecological foundation of genetic, metabolic, and ecosystem health. This paper discusses the fundamental requirements for sustainable food production on the molecular, physiological, and ecological scales, including evolutionary and geological insights, in an attempt to identify the global conditions needed for the primary food production to ensure we survive this century. Particular emphasis is placed on how to make extensive use of this planet’s genetic resources without irretrievably losing them.
Author Correction: Snail collaborates with EGR-1 and SP-1 to directly activate transcription of MMP 9 and ZEB1
Authors: Wu Wen-Sheng , You Ren-In , Cheng Chuan-Chu , Lee Ming-Che , Lin Teng-Yi , Hu Chi-Tan
Published: September 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Architecture-Guided Fluid Flow Directs Renal Biomineralization
Authors: Ho Sunita P. , Chen Ling , Allen Frances I. , Hsi Ryan S. , Shimotake Alex R. , Wiener Scott V. , Kang Misun , Minor Andrew M. , Stoller Marshall L.
Published: September 2018

Nephrocalcinosis often begins on a calcium phosphate deposit, at the tip of the medullo-papillary complex (MPC) known as Randall’s plaque (RP). Contextualizing proximally observed biominerals within the MPC has led us to postulate a mechanobiological switch that can trigger interstitial biomineralization at the MPC tip, remote from the intratubular biominerals. Micro X-ray computed tomography scans of human MPCs correlated with transmission and scanning electron micrographs, and X-ray energy dispersive spectrometry demonstrated novel findings about anatomically-specific biominerals. An abundance of proximal intratubular biominerals were associated with emergence of distal interstitial RP. The fundamental architecture of the MPC and mineral densities at the proximal and distal locations of the MPC differed markedly. A predominance of plate-like minerals or radially oriented plate-like crystallites within spheroidal minerals in the proximal intratubular locations, and core-shell type crystallites within spheroidal minerals in distal interstitial locations were observed. Based on the MPC anatomic location of structure-specific biominerals, a biological switch within the mineral-free zone occurring between the proximal and distal locations is postulated. The “on” and “off” switch is dependent on changes in the pressure differential resulting from changes in tubule diameters; the “Venturi effect” changes the “circumferential strain” and culminates in interstitial crystal deposits in the distal tubule wall in response to proximal tubular obstruction. These distal interstitial mineralizations can emerge into the collecting system of the kidney linking nephrocalcinosis with nephrolithiasis.
Mitochondrial transcription factor A (TFAM) shapes metabolic and invasion gene signatures in melanoma
Authors: Araujo L. F. , Siena A. D. D. , Plaça J. R. , Brotto D. B. , Barros I. I. , Muys B. R. , Biagi C. A. O. , Peronni K. C. , Sousa J. F. , Molfetta G. A. , West L. C. , West A. P. , Leopoldino A. M. , Espreafico E. M. , Silva W. A.
Published: September 2018

Mitochondria are central key players in cell metabolism, and mitochondrial DNA (mtDNA) instability has been linked to metabolic changes that contribute to tumorigenesis and to increased expression of pro-tumorigenic genes. Here, we use melanoma cell lines and metastatic melanoma tumors to evaluate the effect of mtDNA alterations and the expression of the mtDNA packaging factor, TFAM, on energetic metabolism and pro-tumorigenic nuclear gene expression changes. We report a positive correlation between mtDNA copy number, glucose consumption, and ATP production in melanoma cell lines. Gene expression analysis reveals a down-regulation of glycolytic enzymes in cell lines and an up-regulation of amino acid metabolism enzymes in melanoma tumors, suggesting that TFAM may shift melanoma fuel utilization from glycolysis towards amino acid metabolism, especially glutamine. Indeed, proliferation assays reveal that TFAM-down melanoma cell lines display a growth arrest in glutamine-free media, emphasizing that these cells rely more on glutamine metabolism than glycolysis. Finally, our data indicate that TFAM correlates to VEGF expression and may contribute to tumorigenesis by triggering a more invasive gene expression signature. Our findings contribute to the understanding of how TFAM affects melanoma cell metabolism, and they provide new insight into the mechanisms by which TFAM and mtDNA copy number influence melanoma tumorigenesis.
Misfolded SOD1 pathology in sporadic Amyotrophic Lateral Sclerosis
Authors: Paré Bastien , Lehmann Manuela , Beaudin Marie , Nordström Ulrika , Saikali Stephan , Julien Jean-Pierre , Gilthorpe Jonathan D. , Marklund Stefan L. , Cashman Neil R. , Andersen Peter M. , Forsberg Karin , Dupré Nicolas , Gould Peter , Brännström Thomas , Gros-Louis François
Published: September 2018

Aggregation of mutant superoxide dismutase 1 (SOD1) is a pathological hallmark of a subset of familial ALS patients. However, the possible role of misfolded wild type SOD1 in human ALS is highly debated. To ascertain whether or not misfolded SOD1 is a common pathological feature in non-SOD1ALS, we performed a blinded histological and biochemical analysis ofpost mortembrain and spinal cord tissues from 19 sporadic ALS, compared with aSOD1A4V patient as well as Alzheimer’s disease (AD) and non-neurological controls. Multiple conformation- or misfolded-specific antibodies for human SOD1 were compared. These were generated independently by different research groups and were compared using standardized conditions. Five different misSOD1 staining patterns were found consistently in tissue sections from SALS cases and the SOD1 A4V patient, but were essentially absent in AD and non-neurological controls. We have established clear experimental protocols and provide specific guidelines for working, with conformational/misfolded SOD1-specific antibodies. Adherence to these guidelines will aid in the comparison of the results of future studies and better interpretation of staining patterns. This blinded, standardized and unbiased approach provides further support for a possible pathological role of misSOD1 in SALS.
Biomechanical interplay between anisotropic re-organization of cells and the surrounding matrix underlies transition to invasive cancer spread
Authors: Kim Deok-Ho , Ewald Andrew J. , Park JinSeok , Kshitiz  , Kwak Moonkyu , Gray Ryan S. , Su Chia-Yi , Seo Jayhyun , An Steven S. , Levchenko Andre
Published: September 2018

The root cause of cancer mortality and morbidity is the metastatic spread of the primary tumor, but underlying mechanisms remain elusive. Here we investigate biomechanical interactions that may accompany invasive spread of melanoma cells. We find that metastatic cells can exert considerable traction forces and modify local collagen organization within a 3D matrix. When this re-organization is mimicked using a nano-fabricated model of aligned extracellular matrix fibers, metastatic cells, including less invasive melanoma cells, were in turn induced to align, elongate and migrate, guided by the local ridge orientations. Strikingly, we found that this aligned migration of melanoma cells was accompanied by long-range regulation of cytoskeletal remodeling that show anisotropic stiffening in the direction of fiber orientation suggestive of a positive feedback between ECM fiber alignment and forces exerted by cancer cells. Taken together, our findings suggest that the invasive spread of cancer cells can be defined by complex interplay with the surrounding matrix, during which they both modify the matrix and use the matrix alignment as a persistent migration cue, leading to more extensive and rapid invasive spread.
Bandgap reduction of photocatalytic TiO2 nanotube by Cu doping
Authors: Gharaei S. Khajoei , Abbasnejad M. , Maezono Ryo
Published: September 2018

We performed the electronic structure calculations of Cu-doped TiO2 nanotubes by using density functional theory aided by the Hubbard correction (DFT + U). Relative positions of the sub-bands due to the dopants in the band diagram are examined to see if they are properly located within the redox interval. The doping is found to tune the material to be a possible candidate for the photocatalyst by making the bandgap accommodated within the visible and infrared range of the solar spectrum. Among several possibilities of the dopant positions, we found that only the case with the dopant located at the center of nanotube seems preventing from electron-hole recombinations to achieve desired photocatalytic activity with n-type behavior.
Saccadic inhibition interrupts ongoing oculomotor activity to enable the rapid deployment of alternate movement plans
Authors: Salinas Emilio , Stanford Terrence R.
Published: September 2018

Diverse psychophysical and neurophysiological results show that oculomotor networks are continuously active, such that plans for making the next eye movement are always ongoing. So, when new visual information arrives unexpectedly, how are those plans affected? At what point can the new information start guiding an eye movement, and how? Here, based on modeling and simulation results, we make two observations that are relevant to these questions. First, we note that many experiments, including those investigating the phenomenon known as “saccadic inhibition”, are consistent with the idea that sudden-onset stimuli briefly interrupt the gradual rise in neural activity associated with the preparation of an impending saccade. And second, we show that this stimulus-driven interruption is functionally adaptive, but only if perception is fast. In that case, putting on hold an ongoing saccade plan toward location A allows the oculomotor system to initiate a concurrent, alternative plan toward location B (where a stimulus just appeared), deliberate (briefly) on the priority of each target, and determine which plan should continue. Based on physiological data, we estimate that the advantage of this strategy, relative to one in which any plan once initiated must be completed, is of several tens of milliseconds per saccade.
Mechanical loading, an important factor in the evaluation of ion release from bone augmentation materials
Authors: MacDonald Kathleen , Boyd Daniel
Published: September 2018

The controlled release of therapeutic inorganic ions from biomaterials is an emerging area of international research. One of the foci for this research is the development of materials, which spatially and temporally modulate therapeutic release, via controlled degradation in the intended physiological environment. Crucially however, our understanding of the release kinetics for such systems remains limited, particularly with respect to the influence of physiological loading. Consequently, this study was designed to investigate the effect of dynamic mechanical loading on a composite material intended to stabilize, reinforce and strengthen vertebral bodies. The composite material contains a borate glass engineered to release strontium as a therapeutic inorganic ion at clinically relevant levels over extended time periods. It was observed that both cyclic (6 MPa 2 Hz) and static (4.3 MPa) compressive loading significantly increased the release of strontium ions in comparison to the static unloaded case. The observed alterations in ion release kinetics suggest that the mechanical loading of the implantation environment should be considered when evaluating the ion release kinetics.
Essential Nucleoid Associated Protein mIHF (Rv1388) Controls Virulence and Housekeeping Genes in Mycobacterium tuberculosis
Authors: Odermatt Nina T. , Sala Claudia , Benjak Andrej , Cole Stewart T.
Published: September 2018

Tight control of gene expression is crucial for Mycobacterium tuberculosis to adapt to the changing environments encountered when infecting or exiting human cells. While three nucleoid associated proteins (NAPs) EspR, HupB and Lsr2 have been investigated, the role of a fourth, the mycobacterial integration host factor (mIHF), remains elusive. Here, we report a multidisciplinary functional analysis that exploits a conditional mIHF mutant. Gene silencing was bactericidal and resulted in elongated cells devoid of septa, with only one nucleoid. ChIP-sequencing identified 153 broad peaks distributed around the chromosome, which were often situated upstream of transcriptional start sites where EspR also bound. RNA-sequencing showed expression of 209 genes to be heavily affected upon mIHF depletion, including those for many tRNAs, DNA synthesis and virulence pathways. Consistent with NAP function, mIHF acts as a global regulator by directly and indirectly controlling genes required for pathogenesis and for housekeeping functions.
Mechanistic insights into the host-microbe interaction and pathogen exclusion mediated by the Mucus-binding protein of Lactobacillus plantarum
Authors: Singh Kumar Siddharth , Kumar Sudarshan , Mohanty Ashok Kumar , Grover Sunita , Kaushik Jai Kumar
Published: September 2018

Surface adhesins of pathogens and probiotics strains are implicated in mediating the binding of microbes to host. Mucus-binding protein (Mub) is unique to gut inhabiting lactic acid bacteria; however, the precise role of Mub proteins or its structural domains in host-microbial interaction is not well understood. Last two domains (Mubs5s6) of the six mucus-binding domains arranged in tandem at the C-terminus of the Lp_1643 protein of Lactobacillus plantarum was expressed in E. coli. Mubs5s6 showed binding with the rat intestinal mucus, pig gastric mucins and human intestinal tissues. Preincubation of Mubs5s6 with the Caco-2 and HT-29 cell lines inhibited the binding of pathogenic enterotoxigenic E. coli cells to the enterocytes by 68% and 81%, respectively. Pull-down assay suggested Mubs5s6 binding to the host mucosa components like cytokeratins, Hsp90 and Laminin. Mubs5s6 was predicted to possess calcium and glucose binding sites. Binding of Mubs5s6 with these ligands was also experimentally observed. These ligands are known to be associated with pathogenesis suggesting Mub might negotiate pathogens in multiple ways. To study the feasibility of Mubs5s6 delivery in the gut, it was encapsulated in chitosan-sodium tripolyphosphate microspheres with an efficiency of 65% and release up to 85% in near neutral pH zone over a period of 20 hours. Our results show that Mub plays an important role in the host-microbial cross-talk and possesses the potential for pathogen exclusion to a greater extent than mediated by L. plantarum cells. The functional and technological characteristics of Mubs5s6 make it suitable for breaking the host-pathogen interaction.
Lagrangian-like Volume Tracking Paradigm for Mass, Momentum and Energy of Nearshore Tsunamis and Damping Mechanism
Authors: Kim Dae-Hong , Son Sangyoung
Published: September 2018

There is a gap between model- or theory-based research outputs, which suggest that the runup and amplification of nonbreaking waves generally increase as the sea bottom slopes decrease, and field observations, which indicate that tsunami damage has been rarely reported in places with vast continental shelfs. To resolve this contradiction, we propose a Lagrangian-like volume tracking paradigm to describe the energy, mass, and momentum of travelling nearshore tsunamis and apply the paradigm to analyse the tsunami damping mechanism at typical geophysical scales. The results support the following conclusions: (i) The suggested paradigm is consistent with field observations; continental shelfs with long and mild slopes can effectively diminish tsunami impacts. (ii) Potential energy becomes significant due to the energy transformation process on steeply sloped bathymetries. (iii) On mild-sloped bathymetries, tsunami potential and kinetic energies are conserved until breaking occurs. After breaking, undular bores attenuate tsunami energies effectively. (iv) For extended continental shelf bathymetries, more of the tsunami mass is reflected offshore.
Signaling network between the dysregulated expression of microRNAs and mRNAs in propofol-induced developmental neurotoxicity in mice
Authors: Jiang Congshan , Logan Sarah , Yan Yasheng , Inagaki Yasuyoshi , Arzua Thiago , Ma Peizhong , Lu Shemin , Bosnjak Zeljko J. , Bai Xiaowen
Published: September 2018

Mounting evidence has demonstrated that general anesthetics could induce acute neuroapoptosis in developing animals followed by long-term cognitive dysfunction, with the mechanisms remaining largely unknown. The aim of this study was to investigate the effect of the intravenous anesthetic propofol on the profiles of microRNAs (miRNAs) and messenger RNAs (mRNAs), and their interactive signaling networks in the developing mouse hippocampus. Postnatal day 7 (P7) mice were exposed to propofol for 3 hours. Hippocampi were harvested from both P7 (3 hours after exposure) and P60 mice for the analysis of the expression of 726 miRNAs and 24,881 mRNAs, and apoptosis. Long-term memory ability of P60 mice was analyzed using the Morris Water Maze. Propofol induced acute apoptosis in the hippocampus, and impaired memory function of mice. There were 100 altered mRNAs and 18 dysregulated miRNAs in the propofol-treated hippocampi compared with the intralipid-treated control tissues on P7. Bioinformatics analysis of these abnormally expressed genes on P7 indicated that 34 dysregulated miRNA-mRNA target pairs were related to pathological neurological and developmental disorder processes such as cell viability, cell morphology and migration, neural stem cell proliferation and neurogenesis, oligodendrocyte myelination, reactive oxygen species, and calcium signaling. Neonatal propofol exposure also resulted in the abnormal expression of 49 mRNAs and 4 miRNAs in P60 mouse hippocampi. Specifically, bioinformatics analysis indicates that among these dysregulated mRNAs and miRNAs, there were 2 dysregulated miRNA-mRNA targets pairs (Fam46a/miR-363-3p and Rgs3/miR-363-3p) that might be related to the effect of propofol on long-term cognitive function. Collectively, our novel investigation indicates that acute and long-term dysregulated miRNA-mRNA signaling networks potentially participate in propofol-induced developmental neurotoxicity.