bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduced IL-37 gene expression and CD8 T lymphocytes in patients with metastatic breast cancer
Authors: Farahani Najmeh , Mohagheghi Fathollah , Mosayebi Ghasem , Ghazavi Ali , Ganji Ali
Published: February 2024

The exact immunopathological mechanisms in the progression of breast cancer are not clearly understood, but various factors including CD8 T lymphocytes have lethal properties on tumor cells. On the other hand, interleukin-37 (IL-37), as a new member of the IL-1 family, is an anti-inflammatory cytokine. The exact role of IL-37 in breast cancer has not yet been determined. This study aimed to evaluate the CD8 T lymphocytes count and IL-37 gene expression in newly diagnosed breast cancer patients with and without metastasis. In this study, blood samples from 36 metastatic and 36 non-metastatic breast cancer patients and 36 healthy individuals as control were collected. After RNA extraction and cDNA synthesis, the relative gene expression was performed using real-time PCR. Also, counting the CD8 T lymphocytes was done by flow cytometry technique. The results of this study showed that the gene expression of IL-37 in blood samples of metastatic and non-metastatic breast cancer patients was significantly lower than in healthy individuals (P < 0.05). The relative gene expression of the IL-37 in ER+/PR+/HER2+ patients with non-metastatic breast cancer had a significant increase compared to HER2+ patients (P < 0.05). Also, CD8 T lymphocytes count in the samples of patients including non-metastatic and metastatic breast cancer was significantly decreased compared to the healthy individuals (P < 0.05). Our findings provide evidence that IL-37 gene expression and CD8 T lymphocytes count, significantly decreased in non-metastatic and metastatic breast cancer. Considering the possible effects of IL-37 on TCD8 cells in tumor immune responses, more research will be done to benefit from the therapeutic effects of this cytokine in the future.
Cost-benefit Analysis of Rohu (Labeo rohita) Reared in In-pond Raceway System and Commercial Earthen Pond
Authors: Rahman Sk. Asif , Rahman et al M. Aminur , Ferdous Md. Akib Ferdous , Biswas Anusree
Published: February 2024

The present study was conducted to determine the cost and benefits of a commercially important major carp Labeo rohita (Rohu), reared under In-pond Raceway System (IPRS) and Commercial Earthen Pond (CEP) for 90 days from 1 October to 30 December 2021. Rohu is considered to be one of the widely available and highly favorable cultured fish in Bangladesh. However, this is the first comparative study on the cost-benefit analysis of rohu in these two aquaculture systems. In total, 13,000 individuals of healthy L. rohita, weighing from 180 to 190 g were stocked in an IPRS cell having an area of 220 m3 of each cell and the area of pond is 1.38 acre, while in the CEP of 1.38 acre was stocked with 5,500 individuals of the same species and same size. A commercial Afil fish feed was used during the experiment. The fishes were fed 3 times at 4 hours of interval in the IPRS cell and 2 times at 12 hours of interval in CEP, respectively during day times. After stocking, all fishes in the IPRS cell were fed at the rate of 5.5-6.0% of body weight for the first 15 days, 5.0-5.5% for the next 15 days, 4.5-5.0% for the next 15 days, 4.0-4.5% for the next 15 days, 3.5-4.0% for the next 15 days and 3.0-3.5% for the last 15 days, while fishes in the CEP were supplemented with the same feed at 4.5-5.0% for the first 30 days, 3.5-4.0% for the next 30 days and 2.5-3.0% for the remaining 30 days. The mean water quality parameters such as temperature, pH, DO and ammonia-nitrogen were 25.34±4.56°C, 7.8±0.34, 6.62±0.34 mg/L and 0.03±0.01 mg/L in IPRS, and 26.04±4.53°C, 7.57±0.28, 5.41±0.20 mg/L and 0.39±0.26 mg/L in CEP, respectively. At the end of the 90-day rearing experiment, total production of rohu fish was obtained to be 9,295 kg and 2,814 kg in IPRS and CEP, respectively. The estimated total costs and net benefits were BDT 9,20,059 and 5,20,665, and BDT 3,52,679 and 69,473 in IPRS and CEP in this order. The cost-benefit ratio in IPRS and CEP was found to be 1.66 and 1.28, respectively. The findings from our study revealed that IPRS is better than CEP for the rearing of L. rohita in respects of higher production and net benefits.
Physico-chemical parameters and antioxidant activity of baked product fortified with fruit waste powder
Authors: Morina Ariol , Shehaj Alketa
Published: February 2024

Fruit wastes are naturally enriched with vitamins, minerals and other bioactive compounds. Compelling evidences justify and designate peels and relative extracts of numerous fruits as nutraceuticals and functional food. Pomegranate (Punica granatum L.) rind is known as a good source of biologically active food components, and in this paper thepotential use of pomegranate rind powder in cookies was studied. Cookies were produced by substituting 8, 16, 23, 31, and 39% of wheat flour with pomegranate rind powder. Chemical parameters (total acidity, ash, total phenolic and flavonoid content, as well as antioxidant activity (using ABTS method), were evaluated in cookies through the comparison to the control sample with no added pomegranate rind powder. Total ash content increased from 0.65% for cookies S0 (0% PoR) to 1.57% for sample S5 (39% PoR), while moisture content decreased from 6.65% to 4.86% for sample S0 and S5 respectively. Total phenolic content ranged from 294.67 mgGAE/100g to 2180.6 mgGAE/100g and flavonoid content from 118.8 mgCE/100g to 1088 mgCE/100g for S1 (8%) and S5 (39%), respectively. All cookies supplemented with PoR powder exhibited higher total phenolic, flavonoid content, and antioxidant activities compare to control sample.
Evaluation of quality parameters in some types of wheat flour used for different purposes
Authors: Shehaj Alketa , Marku Klotilda , Morina Ariola , Rama Albes
Published: February 2024

Wheat flour is generally produced by milling wheat until a fine powder is produced. The flour is used for different purposes, generally for the preparation of baked products. This study aims to analyze and evaluate the quality of the flour that is traded on the market in Albania, such as T00, T0, all-purpose, whole grain, etc. produced in Albania or abroad. A total of 20 flour samples were purchased from the market and the technical properties such as water absorption, stability, sedimentation, dough energy and some physical and chemical properties such as moisture, total ash, acidity, protein and gluten were evaluated. Analyses were conducted according to AACC standards. The results show that all samples have almost the same parameters as described on the labels. Protein content ranged from 9.6 to 16.6%, with the highest percentage found in sample IFW0. Water absorption ranged from 58.5 to 65%, with sample AFA1 having the highest value. Acidity is the most commonly used parameter to determine storage conditions, and all samples had a low value. It ranged from 0.65 to 0.8%, with the highest value found in whole wheat flour. The gluten content varied from 18 to 35.7%, with the highest value detected in sample IFW0. According to the analysis of the samples, the wheat flour sold in the Albanian market has good parameters regarding the amount of protein, gluten, water absorption etc. They are different for different types of flours and we recommend consumers to read the label carefully before buying.
OF GODS AND MONSTERS: NATIONAL SECURITY AND CANADIAN REFUGEE POLICY
Authors: Aiken Sharryn J.
Published: February 2024

The fiftieth anniversary year of the 1951 Convention affords an appropriate juncture to turn our gaze to the pledges Canada has made as a signatory state and the extent to which Canadian refugee policy has been “securitized” at the expense of vulnerable refugees and the very objectives the Convention was designed to address. Through the lens of the legal standards established by the Convention as well as complementary international norms and jurisprudence, this paper considers Canada's contemporary record on refugee issues with specific reference to the national security dimension of domestic policy. The author begins by tracing the evolution of refugee law and policy during the Cold War period, as well as parallel developments in the area of immigration security. The primary focus then turns to the anti-terrorism and security measures implemented by the federal government in 1992, together with proposals for reform under review in the Canadian Senate. The author concludes by locating the coordinates of an alternative approach to national security, one which incorporates the legal standards and normative values codified in the Refugee Convention. It is an approach that is premised on the overarching objective of bridging the chasm between “civilized self” and “barbaric other,” of enhancing human security for refugees and host population alike.
L’ORGANISATION INTERNATIONALE DE PROTECTION CIVILE OU LE DIFFICILE ACCÈS AU STATUT D’INSTITUTION SPÉCIALISÉE DES NATIONS UNIES
Authors: Le Jeune Pierrick
Published: February 2024

L’Organisation Internationale de Protection Civile, organisation intergouvernementale créée il y a maintenant trente ans, est candidate au statut d’institution spécialisée des Nations Unies. L’Organisation des Nations Unies a constitué un réseau d’institutions spécialisées, moyen efficace, déterminant et rationnel d’action dans le domaine de la collaboration technique. L’OIPC, qui sollicite le bénéfice de ce statut, doit s’adapter aux différents critères exigés des différentes institutions spécialisées. Les procédures d’accès au statut ont varié selon la période, selon le type d’organisation. Divers textes fixent les dispositions applicables, en prévoyant plusieurs étapes garantissant un examen attentif de la candidature. En revanche, même si les textes sont clairs, la pratique semble plus délicate dans la mesure où les aspects politiques peuvent être pris en considération avant les modalités ou exigences techniques. Pour bénéficier du statut et fonctionner selon les critères des institutions spécialisées, l’OIPC devra ajuster son organisation et son fonctionnement, notamment pour ce qui concerne les représentants des États membres et le statut des personnels, mais également pour ce qui touche aux questions budgétaires et financières.
MONSANTO v. GOVERNMENT OF CANADA? NAFTA AND THE RBST CONTROVERSY: A CANADIAN PERSPECTIVE
Authors: Gibson Kevin
Published: February 2024

Le Chapitre 11 de l’Accord de Libre-échange Nord Américain est probablement devenu avec le temps l’une des portions de l’entente de libre-échange ayant suscité le plus de réactions et entraîné le plus de polémiques, tant au plan juridique que social. A cet égard, le présent article tentera d’examiner la controverse entourant le récent refus de Santé Canada d’autoriser en territoire canadien la vente et la commercialisation du rBST, produit fabriqué par la compagnie Monsanto et autrement connu sous le nom de « Nutrilac ». Décision d’ailleurs contestée par la corporation américaine en vertu des dispositions de l’ALÉNA. Or, le choix par Monsanto et le Canada du mécanisme prévu au chapitre 11 s’explique non seulement parce qu’il est le plus naturel dans un contexte nord-américain de règlement des différends commerciaux, mais aussi, à la lumière d’un examen d’ensemble de l’ALÉNA, parce qu’il est susceptible de fournir assez de souplesse aux parties pour arriver à une entente pouvant satisfaire à la fois la partie privée et publique. Cela dit, pour bien mesurer la portée du chapitre 11 de l’ALÉNA et son impact sur le gouvernement fédéral, il est utile de comparer ici l’affaire impliquant Monsanto avec la récente Affaire du boeuf aux hormones en Europe et dont le différend fut porté cette fois devant l’organe de règlement des différends de l’OMC.
ENJEUX ET PERSPECTIVES
Authors: Decaux Emmanuel
Published: February 2024

La Convention européenne est au carrefour de deux grandes idées qui ont marqué l’après-guerre, la construction européenne et la protection des droits de l’Homme. Depuis 50 ans, la Cour européenne a construit une jurisprudence riche de plus d’un millier d’arrêts qui concerne désormais 41 États parties à travers une Europe libre et réunie. Pour autant, la Convention se trouve menacée, de l’intérieur, par la démission politique des États face aux violations massives des droits de l’Homme, et de l’extérieur, par le développement du noyau dur de l’Union européenne et le risque de double standards dans une Europe à deux vitesses. Seule la réaffirmation de l’universalité et de l’indivisibilité des droits de l’Homme peut permettre de surmonter ces contradictions pour être fidèle à l’oeuvre des Pères fondateurs.
COMMON LAW, « CIVIL LAW » ET DROIT PÉNAL INTERNATIONAL : TANGO (LE DERNIER ?) À LA HAYE
Authors: Schabas William A.
Published: February 2024

Les systèmes de common law, puis de droit continental ou romano-germanique, offrent à la procédure criminelle deux approches très différentes. Ces systèmes se rencontrent dans le nouveau domaine, en constante évolution, du droit pénal international où les juristes des deux systèmes s’efforcent de créer un nouveau modèle. Dans ce contexte, on doit faire face aux contributions, et aux incompréhensions, qui proviennent d’un tel processus.

Le développement d’un système international prend aussi place dans un contexte de respect international des garanties judiciaires prévues dans les instruments de protection des droits de la personne. Enfin, les exigences spécifiques de la justice internationale influence le modèle procédural. Ces trois thèmes sont abordés à la lumière de la pratique des deux tribunaux ad hoc, pour l’ex-Yougoslavie et le Rwanda, puis de la Cour pénale internationale et du Statut de Rome.
LE MILITANTISME JURIDIQUE ET LE NÉO-NATURALISME FACE AU DROIT INTERNATIONAL POSITIF : LES FLUX MASSIFS DE RÉFUGIÉS ET LA SÉCURITÉ NATIONALE
Authors: Barutciski Michael
Published: February 2024

Cet article souligne les divergences entre les interprétations des normes juridiques en droit des réfugiés proposées par les gouvernements et les militants. En s’appuyant sur l’exemple des obligations d’un État d’accueil confronté par un flux massif déstabilisant, il suggère que les instances judiciaires ont tendance à rejeter l’argumentation récente de certains militants concernant des principes fondamentaux de protection.
ECHOES OF THE OLD COUNTRIES OR BRAVE NEW WORLDS? LEGAL RESPONSES TO REFUGEES AND ASYLUM SEEKERS IN AUSTRALIA AND NEW ZEALAND
Authors: Crock Mary
Published: February 2024

In spite of their colonial origins and their continuing ties with Great Britain and Europe, it is only recently that Australia and New Zealand have begun to think in global terms about immigration control and the challenges posed by asylum seekers. The experience of unauthorized migration in these two countries has been somewhat different. Nevertheless, both are now feeling the effects of the burgeoning industry of people smuggling. The closure of traditional migration routes throughout Europe brought about by the harmonization of laws and practice within the European Union may be one factor in the rise of unauthorized migration in the Asia Pacific region. While European laws and policies rarely rate a mention in the refugee discourse in this part of the world, the response to the mobile asylum seeker phenomenon reveals many resonances with the approaches adopted in the “old World” of the European Union – and, more recently, in the United States. This paper argues that, in Australia’s case, some “borrowings” from Europe and from North America have been inappropriate for this region. Far from evincing a commitment to global solutions and rationalized responses to humanitarian crises, the Australian initiatives suggest a country immersed in local concerns and self-interest. In spite of its tiny size and geographical isolation, the greater openness of New Zealand’s laws provides some interesting contrast material. Of equal interest, however, is the attention the world is beginning to pay to Australia’s asylum laws – most particularly those relating to the detention and removal of asylum seekers who come as unauthorized arrivals.
WORLD ORDER AND UNHCR'S “COMPREHENSIVE” APPROACH TO REFUGEES
Authors: Lui Robyn
Published: February 2024

Within the context of the changing dynamics of displacement and the increasing complexity of humanitarian issues, UNHCR distinguishes the “reactive, exile-oriented and refugee specific” activities during its early years with the “proactive, home-land oriented and holistic” activities of recent times. The task of this paper is to be explicit about the conditions under which explanations of refugee issues, particularly the concepts of international protection and durable solution are being transformed. The article also examines UNHCR’s humanitarian agenda as a response to the global refugee crisis.
LA PROTECTION INTERNATIONALE DES RÉFUGIÉS ET LE PARTAGE DU FARDEAU : LEÇONS DE LA CRISE DU KOSOVO
Authors: Barutciski Michael , Suhrke Astri
Published: February 2024

Le principal défi politique de la crise des réfugiés du Kosovo était de convaincre la Macédoine d’admettre un flux massif de réfugiés qui représentait une menace à sa stabilité. La solution éventuelle reposait sur un mécanisme de « partage du fardeau » impliquant le transfert de réfugiés vers des pays tiers. Nombreux militants des droits de l’homme ont soutenu que le gouvernement macédonien devait permettre l’entrée des réfugiés de façon inconditionnelle. Ils affirmaient que toute conditionnalité compromettrait le principe du premier asile et encouragerait les politiques restrictives envers les réfugiés. D’autres observateurs considéraient que le refus macédonien représentait un fait politique qu’il fallait reconnaître afin d’arriver à une solution pour éviter une catastrophe humanitaire à la frontière. Ces deux approches se sont affrontées pendant que les États et les organisations internationales essayaient de résoudre la crise des réfugiés bloqués sur la frontière du Kosovo. Cet article propose une troisième approche qui tente de concilier les camps opposés. Il présente des arguments juridiques qui suggèrent que le premier asile ne représente pas une obligation inconditionnelle imposée sur tous les États dans toutes les situations. Il avance également des arguments moraux et politiques pour encourager les États à partager le fardeau des réfugiés envers lesquels ils ont une obligation spéciale. La reconnaissance de tels cas exceptionnels contribuerait à renforcer l’efficacité du système international de protection des réfugiés. La crise du Kosovo suggère qu’un tel cas exceptionnel, pour lequel le partage du fardeau peut s’avérer nécessaire, se présente quand un État vulnérable est confronté à un flux massif qui risque d’étendre le conflit sur son territoire et de mener à une déstabilisation grave du pays.
CONSOLIDATED DECISION-MAKING: THE CANADIAN EXPERIENCE
Authors: VanKessel Gerry
Published: February 2024

As part to the 1951 Convention and its 1967 Protocol, Canada is obliged to protect persons on its territory who have a well founded fear of persecution based on their nationality, membership in a social group, or political opinion. Inspite of the fact that the Convention refugee definition has been fully incorporated into the Immigration Act, the process of determining refugee status and protection needs in Canada has been criticized by various organizations including the Auditor General of Canada and the Legislative Review Advisory Group. The recommendations made by the Auditor General include that Citizenship and Immigration should ensure that the risk of return review is within the scope of the objectives set out for the Post-Determination Refugee Class and that it is carried out in an efficient and timely manner. The Legislative Review Advisory Group found that not only the current system was complex, but also that some of Canada’s international commitments have not been fully incorporated into domestic legislation. It was determined that the Immigration and Refugee Board would become responsible for applying all protection criteria in a consolidated protection definition, and, hence, would be the expert body to administer this definition. A single process in which all the facts are before the same decision-maker will promote fairness, consistency and efficiency.
LES LIMITES À LA COMPÉTENCE INTERNATIONALE DES TRIBUNAUX QUÉBÉCOIS
Authors: Saumier Geneviève
Published: February 2024

Il existe trois moyens pour un défendeur de s’opposer à la compétence internationale des tribunaux québécois. Le défendeur peut prétendre que les faits ne répondent pas aux critères juridictionnels du Droit international privé tels qu’énoncés dans le Livre X du Code civil. Il peut aussi démontrer que bien que le tribunal québécois soit prima facie compétent en vertu du Code civil, il n’existe pas de lien réel et substantiel entre le tribunal et le litige. Finalement, le défendeur peut invoquer le forum non conveniens par l’intermédiaire de l’article 3135 C.c.Q., c’est-à-dire demander au tribunal de décliner l’exercice de sa compétence.

Ces trois moyens doivent être exercés à l’intérieur d’un délai variant selon que la procédure soit ordinaire ou allégée. Dans la voie ordinaire, la règle générale est que la requête en exception déclinatoire soit signifiée, selon les articles 161 et 163 C.p.c. dans les cinq jours de la date prévue pour comparaître, depuis l’arrêt Alimport c. Victoria Transport Ltd. L’incompétence du tribunal québécois relevant d’une clause d’arbitrage ou d’une clause d’élection de for sont cependant des exceptions à cette règle. En procédure allégée, l’article 481.7 C.p.c. prévoit que le défendeur doit proposer ses moyens déclinatoires « dans les dix jours suivant le délai de comparution ». L’arrêt Corporation Internationale Brother c. S.T.D. Systems Inc. indique cependant qu’il ne s’agit pas d’un délai de rigueur, le tribunal pouvant proroger ce délai.

Les différences des régimes de délai applicable selon que l’on se trouve dans une procédure ordinaire ou allégée n’est qu’un des motifs justifiant une révision en profondeur de la procédure à suivre pour s’opposer à la compétence internationale des tribunaux québécois.
SÉCURITÉ ENVIRONNEMENTALE ET INSÉCURITÉSINTERNATIONALES
Authors: Le Prestre Philippe
Published: February 2024

Cet essai explore les liens entre la dégradation de l’environnement et l’insécurité internationale. Les travaux sur cette notion font référence à quatre approches distinctes selon que l’objet d’étude soit l’environnement, l’individu, l’État ou le système international. Dans ce dernier cas, on peut identifier quatre séries d’hypothèses reliant la dégradation de l’environnement et les insécurités internationales : i) certaines activités d’un État à l’égard d’une ressource essentielle peuvent être jugées menaçantes par un autre État; ii) des instabilités internes engendrées par la dégradation de l’environnement peuvent déborder au delà des frontières; iii) la protection de l’environnement peut servir de prétexte à la poursuite d’objectifs de puissance traditionnels; et iv) l’état de l’environnement peut être évoqué afin de gagner un soutien international à des objectifs politiques internes traditionnels.

En conclusion, l’apport analytique de la notion de sécurité environnementale est jugé plutôt faible. Toutefois, ses dimensions instrumentales et psychosociologiques méritent plus d’attention. Si l’environnement peut devenir source de conflits, c’est dans la mesure où les changements environnementaux favorisent l’émergence d’un sentiment d’insécurité qui peut être utilisé comme instrument de politique intérieure ou extérieure.
DE L’ANC À LA CONSTITUTION SUD-AFRICAINE : CONTINUITÉ OU RUPTURE DANS LA PROTECTION DES DROITS FONDAMENTAUX ?
Authors: Barry Ousmane
Published: February 2024

La population d’Afrique du Sud fut longtemps divisée par la ségrégation raciale. Inspiré par la nouvelle ère des droits de la personne et de la démocratie, un mouvement s’éleva pour condamner l’apartheid tant au niveau national qu’international. D’abord, l’Assemblée générale puis, le Conseil de sécurité, suite aux appels pressants des États africains et asiatiques, firent pression pour exclure l’Afrique du Sud des organisations internationales tant et aussi longtemps que le régime perdurerait. Ces revendications amenèrent l’isolement diplomatique complet de l’Afrique du Sud le 12 novembre 1974, isolement qui persista jusqu’à l’année 1994 et qui fut accompagné par une lutte acharnée contre l’apartheid. Après vingt ans d’isolement, l’Afrique du Sud abolit sa politique de ségrégation et effectua un remaniement complet de son régime pour enfin être réintégrée dans la légalité internationale et admise à titre de participant effectif aux organisations intergouvemementales.

Cette évolution, à la fois historique et politique, a mené à la consécration des droits fondamentaux dans le dispositif interne de l’Afrique du Sud par le rejet de l’ethnocentrisme et du racisme sous toutes ses formes et par l’adhésion à un modèle d’unité « dans la diversité ». Ce modèle – produit d’une Constitution regroupant neuf provinces multiethniques et basée sur l’expression de l’autodétermination des populations sud-africaines – ne pourra toutefois demeurer viable que par la participation démocratique des populations et la réalisation de leur droit au développement. Il est nécessaire de promouvoir le développement économique national et d’adopter une politique de réduction des inégalités.
From John Cage to the Outdoor School: Activating the “Minor” through Mycological Forays
Authors: Legassie Treva Michelle
Published: February 2024

Dans la foulée des réflexions d’Erin Manning et Brian Massumi conceptualisant la recherche-création en tant qu’expression de ce qui est de l’ordre du mineur, le présent article propose une exploration du rituel créatif de l’incursion mycologique en tant que recherche-création. L’incursion, comme la recherche-création, perturbe les principaux systèmes régissant les méthodes institutionnelles (universitaires, scientifiques, anthropologiques, artistiques) et s’attarde aux rencontres fortuites indéterminées qui surviennent lors de la quête de champignons. Cet article établit un lien entre l’intérêt que le compositeur américain John Cage a entretenu toute sa vie pour les champignons et les incursions contemporaines dirigées par le commissaire et écrivain Amish Morrell et la créatrice en art visuel et en performance Diane Borsato, ainsi que le travail de revitalisation écologique du collectif japonais, Matsutake Crusaders.
Theoretical Analysis of the Problem of Formation of Professional Readiness of Employees of the Ministry of Internal Affairs of Russia to Perform Official Duties
Authors: Sadekov Rustem Rafekovich
Published: February 2024

The author considers in detail such aspects in his work, which are devoted to the system of psychological support in the learning process. The study of the influence of the mental health of employees of the internal affairs bodies of the Russian Federation on their work productivity and communication in the service team. The subject of the research in the presented work was the process of professional education and training for law enforcement officers in various conditions. The purpose of the study was to determine the features of the formation of professional skills of employees of the internal affairs bodies of the Russian Federation. The object of the study was the professional skill formed by law enforcement officers in the process of performing official duties. The main conclusions of the study are the assumptions that the readiness of employees of the Ministry of Internal Affairs of Russia is often formed under the influence of various factors, circumstances and conditions. As the main ones, the author identified such as the development of professional motivation, psychological readiness to work in conditions associated with increased loads and peculiarities of service, awareness of the value of human and citizen life, the formation of verbal and non-verbal communication culture, the formation of tolerance to stressful situations, the absence of excessive requirements. The work is based on the analysis of fundamental and modern research on this issue, processing and drafting of modern provisions for training law enforcement officers to perform official duties.
Pharmacologic hyperstabilisation of the HIV-1 capsid lattice induces capsid failure
Authors: Faysal KM Rifat , Walsh James C , Renner Nadine , Márquez Chantal L , Shah Vaibhav B , Tuckwell Andrew J , Christie Michelle P , Parker Michael W , Turville Stuart G , Towers Greg J , James Leo C , Jacques David A , Böcking Till
Published: February 2024

The HIV-1 capsid has emerged as a tractable target for antiretroviral therapy. Lenacapavir, developed by Gilead Sciences, is the first capsid-targeting drug approved for medical use. Here, we investigate the effect of lenacapavir on HIV capsid stability and uncoating. We employ a single particle approach that simultaneously measures capsid content release and lattice persistence. We demonstrate that lenacapavir’s potent antiviral activity is predominantly due to lethal hyperstabilisation of the capsid lattice and resultant loss of compartmentalisation. This study highlights that disrupting capsid metastability is a powerful strategy for the development of novel antivirals.
Improving PD-1 blockade plus chemotherapy for complete remission of lung cancer by nanoPDLIM2
Authors: Sun Fan , Yan Pengrong , Xiao Yadong , Zhang Hongqiao , Shapiro Steven D. , Xiao Gutian , Qu Zhaoxia
Published: February 2024

Immune checkpoint inhibitors (ICIs) and their combination with other therapies such as chemotherapy, fail in most cancer patients. We previously identified the PDZ-LIM domain-containing protein 2 (PDLIM2) as a
bona fide
tumor suppressor that is repressed in lung cancer to drive cancer and its chemo and immunotherapy resistance, suggesting a new target for lung cancer therapy improvement.Human clinical samples and data were used to investigate
PDLIM2
genetic and epigenetic changes in lung cancer. Using an endogenous mouse lung cancer model faithfully recapitulating refractory human lung cancer and a clinically feasible nano-delivery system, we investigated the therapeutic efficacy, action mechanism, and safety of systemically administrated PDLIM2 expression plasmids encapsulated in nanoparticles (nanoPDLIM2) and its combination with PD-1 antibody and chemotherapeutic drugs.PDLIM2 repression in human lung cancer involves both genetic deletion and epigenetic alteration. NanoPDLIM2 showed low toxicity, high tumor specificity, antitumor activity, and greatly improved the efficacy of anti-PD-1 and chemotherapeutic drugs, with complete tumor remission in most mice and substantial tumor reduction in the remaining mice by their triple combination. Mechanistically, nanoPDLIM2 increased major histocompatibility complex class I (MHC-I) expression, suppressed multi-drug resistance 1 (MDR1) induction and survival genes and other tumor-related genes expression in tumor cells, and enhanced lymphocyte tumor infiltration, turning the cold tumors hot and sensitive to ICIs and rendering them vulnerable to chemotherapeutic drugs and activated tumor-infiltrating lymphocytes (TILs) including those unleashed by ICIs.These studies established a clinically applicable PDLIM2-based combination therapy with great efficacy for lung cancer and possibly other cold cancers.
Memory-specific encoding activities of the ventral tegmental area dopamine and GABA neurons
Authors: Glykos Vasileios , Fujisawa Shigeyoshi
Published: February 2024

Although the midbrain dopamine (DA) system plays a crucial role in higher cognitive functions, including updating and maintaining short-term memory, the encoding properties of the somatic spiking activity of ventral tegmental area (VTA) DA neurons for short-term memory computations have not yet been identified. Here, we probed and analyzed the activity of optogenetically identified DA and GABA neurons while mice engaged in short-term memory-dependent behavior in a T-maze task. Single-neuron analysis revealed that significant subpopulations of DA and GABA neurons responded differently between left and right trials in the memory delay. With a series of control behavioral tasks and regression analysis tools, we show that firing rate differences are linked to short-term memory-dependent decisions and cannot be explained by reward-related processes, motivated behavior, or motor-related activities. This evidence provides novel insights into the mnemonic encoding activities of midbrain DA and GABA neurons.
Structural and biophysical analysis of a Haemophilus influenzae tripartite ATP-independent periplasmic (TRAP) transporter
Authors: Currie Michael J , Davies James S , Scalise Mariafrancesca , Gulati Ashutosh , Wright Joshua D , Newton-Vesty Michael C , Abeysekera Gayan S , Subramanian Ramaswamy , Wahlgren Weixiao Y , Friemann Rosmarie , Allison Jane R , Mace Peter D , Griffin Michael DW , Demeler Borries , Wakatsuki Soichi , Drew David , Indiveri Cesare , Dobson Renwick CJ , North Rachel A
Published: February 2024

Tripartite ATP-independent periplasmic (TRAP) transporters are secondary-active transporters that receive their substrates via a soluble-binding protein to move bioorganic acids across bacterial or archaeal cell membranes. Recent cryo-electron microscopy (cryo-EM) structures of TRAP transporters provide a broad framework to understand how they work, but the mechanistic details of transport are not yet defined. Here we report the cryo-EM structure of the Haemophilus influenzae N-acetylneuraminate TRAP transporter (HiSiaQM) at 2.99 Å resolution (extending to 2.2 Å at the core), revealing new features. The improved resolution (the previous HiSiaQM structure is 4.7 Å resolution) permits accurate assignment of two Na+ sites and the architecture of the substrate-binding site, consistent with mutagenic and functional data. Moreover, rather than a monomer, the HiSiaQM structure is a homodimer. We observe lipids at the dimer interface, as well as a lipid trapped within the fusion that links the SiaQ and SiaM subunits. We show that the affinity (KD) for the complex between the soluble HiSiaP protein and HiSiaQM is in the micromolar range and that a related SiaP can bind HiSiaQM. This work provides key data that enhances our understanding of the ‘elevator-with-an-operator’ mechanism of TRAP transporters.
Salmonella-induced SIRT1 and SIRT3 are crucial for maintaining the metabolic switch in bacteria and host for successful pathogenesis
Authors: Hajra Dipasree , Rajmani Raju S , Chaudhary Ayushi Devendrasingh , Gupta Shashi Kumar , Chakravortty Dipshikha
Published: February 2024

Sirtuins are the major players in host immunometabolic regulation. However, the role of sirtuins in the modulation of the immune metabolism pertaining to salmonellosis is largely unknown. Here, our investigation focussed on the role of two important sirtuins, SIRT1 and SIRT3, shedding light on their impact on intracellular Salmonella’s metabolic switch and pathogenesis establishment. Our study indicated the ability of the live Salmonella Typhimurium to differentially regulate the levels of SIRT1 and SIRT3 for maintaining the high glycolytic metabolism and low fatty acid metabolism in Salmonella. Perturbing SIRT1 or SIRT3 through knockdown or inhibition resulted in a remarkable shift in the host metabolism to low fatty acid oxidation and high glycolysis. This switch led to decreased proliferation of Salmonella in the macrophages. Further, Salmonella-induced higher levels of SIRT1 and SIRT3 led to a skewed polarization state of the macrophages from a pro-inflammatory M1 state toward an immunosuppressive M2, making it more conducive for the intracellular life of Salmonella. Alongside, governing immunological functions by modulating p65 NF-κB acetylation, SIRT1, and SIRT3 also skew Salmonella-induced host metabolic switch by regulating the acetylation status of HIF-1α and PDHA1. Interestingly, though knockdown of SIRT1/3 attenuated Salmonella proliferation in macrophages, in in vivo mice model of infection, inhibition or knockdown of SIRT1/3 led to more dissemination and higher organ burden, which can be attributed to enhanced ROS and IL-6 production. Our study hence reports for the first time that Salmonella modulates SIRT1/3 levels to maintain its own metabolism for successful pathogenesis.
Detecting, mapping, and suppressing the spread of a decade-long Pseudomonas aeruginosa nosocomial outbreak with genomics
Authors: Stribling William , Hall Lindsey R. , Powell Aubrey , Harless Casey , Martin Melissa J. , Corey Brendan W. , Snesrud Erik , Ong Ana , Maybank Rosslyn , Stam Jason , Bartlett Katie , Jones Brendan T. , Preston Lan N. , Lane Katherine F. , Thompson Bernadette , Young Lynn M. , Kwak Yoon I. , Barsoumian Alice E. , Markelz Ana-Elizabeth , Kiley John L. , Cybulski Robert J. , Bennett Jason W. , Mc Gann Patrick T. , Lebreton Francois
Published: February 2024

Whole-genome sequencing is revolutionizing bacterial outbreak investigation but its application to the clinic remains limited. In 2020, prospective and retrospective surveillance detected a
Pseudomonas aeruginosa
outbreak with 254 isolates collected from 82 patients in 27 wards of a hospital. Its origin was dated to the late 90s, just after the facility opened, and patient-to-patient and environment-to-patient cases of transmission were inferred. Over time, two epidemic subclones evolved in separate hosts and hospital areas, including newly opened wards, and hospital-wide sampling confirmed reservoirs persisted in the plumbing. Pathoadaptive mutations in genes associated with virulence, cell wall biogenesis, and antibiotic resistance were identified. While the latter correlated with the acquisition of phenotypic resistances to 1st (cephalosporin), 2nd (carbapenems) and 3rd (colistin) lines of treatment, maximum parsimony suggested that a truncation in a lipopolysaccharide component coincided with the emergence of a subclone prevalent in chronic infections. Since initial identification, extensive infection control efforts guided by routine, near real-time surveillance have proved successful at slowing transmission.Every year, millions of hospital-associated infections are threatening patient lives. This, in a world in which rates of resistances to existing antibiotics are increasing. And this, at a time dubbed the post-antibiotic era when new drugs are scarce. But now is also the golden age of genomics. Here, applying this transformative technology to the clinic revealed an outbreak of
Pseudomonas aeruginosa
, resistant to last line antibiotics, that had escaped detection for decades. The mapping of transmission chains, through hospital floors, pointed to environmental reservoirs in intensive care units but also provided critical insights into the evolution and adaptation of this pathogen. Genomic data, shared in near real-time with the hospital, resulted in targeted interventions and the prevention of new cases.
Visuo-motor updating in autism symptomatology
Authors: Pomè Antonella , Zimmermann Eckart
Published: February 2024

Autism Spectrum Disorder (ASD) presents a range of challenges, including heightened sensory sensitivities. Here, we examine the idea that sensory overload in ASD may be linked to issues with efference copy mechanisms, which predict the sensory outcomes of self-generated actions, such as eye movements. Efference copies play a vital role in maintaining visual and motor stability. Disrupted efference copies hinder precise predictions, leading to increased reliance on actual feedback and potential distortions in perceptions across eye movements. In our first experiment, we tested how well individuals with varying levels of autistic traits updated their mental map after making eye movements. We found that those with more autistic traits had difficulty using information from their eye movements to update the spatial representation of their mental map, resulting in significant errors in object localization. In the second experiment, we looked at how participants perceived an object displacement after making eye movements. Using a trans-saccadic spatial updating task, we found that those with higher autism scores exhibited a greater bias, indicating under-compensation of eye movements and a failure to maintain spatial stability during saccades. Overall, our study underscores efference copy’s vital role in visuo-motor stability, aligning with Bayesian theories of autism, potentially informing interventions for improved action-perception integration in autism.
Metabolite profiling of human renal cell carcinoma reveals tissue-origin dominance in nutrient availability
Authors: Abbott Keene L. , Ali Ahmed , Reinfeld Bradley I. , Deik Amy , Subudhi Sonu , Landis Madelyn D. , Hongo Rachel A. , Young Kirsten L. , Kunchok Tenzin , Nabel Christopher S. , Crowder Kayla D. , Kent Johnathan R. , Madariaga Maria Lucia L. , Jain Rakesh K. , Beckermann Kathryn E. , Lewis Caroline A. , Clish Clary B. , Muir Alexander , Rathmell W. Kimryn , Rathmell Jeffrey C. , Heiden Matthew G. Vander
Published: February 2024

The tumor microenvironment is a determinant of cancer progression and therapeutic efficacy, with nutrient availability playing an important role. Although it is established that the local abundance of specific nutrients defines the metabolic parameters for tumor growth, the factors guiding nutrient availability in tumor compared to normal tissue and blood remain poorly understood. To define these factors in renal cell carcinoma (RCC), we performed quantitative metabolomic and comprehensive lipidomic analyses of tumor interstitial fluid (TIF), adjacent normal kidney interstitial fluid (KIF), and plasma samples collected from patients. TIF nutrient composition closely resembles KIF, suggesting that tissue-specific factors unrelated to the presence of cancer exert a stronger influence on nutrient levels than tumor-driven alterations. Notably, select metabolite changes consistent with known features of RCC metabolism are found in RCC TIF, while glucose levels in TIF are not depleted to levels that are lower than those found in KIF. These findings inform tissue nutrient dynamics in RCC, highlighting a dominant role of non-cancer driven tissue factors in shaping nutrient availability in these tumors.
Expression patterns of E2Fs identify tumor microenvironment features in human gastric cancer
Authors: Li Fanni , Yan Jun , Leng Jing , Yu Tianyu , Zhou Huayou , Liu Chang , Huang Wenbo , Sun Qi , Zhao Wei
Published: February 2024

Objective

E2F transcription factors are associated with tumor development, but their underlying mechanisms in gastric cancer (GC) remain unclear. This study explored whether E2Fs determine the prognosis or immune and therapy responses of GC patients.

Methods

E2F regulation patterns from The Cancer Genome Atlas (TCGA) were systematically investigated and E2F patterns were correlated with the characteristics of cellular infiltration in the tumor microenvironment (TME). A principal component analysis was used to construct an E2F scoring model based on prognosis-related differential genes to quantify the E2F regulation of a single tumor. This scoring model was then tested in patient cohorts to predict effects of immunotherapy.

Results

Based on the expression profiles of E2F transcription factors in GC, two different regulatory patterns of E2F were identified. TME and survival differences emerged between the two clusters. Lower survival rates in the Cluster2 group were attributed to limited immune function due to stromal activation. The E2F scoring model was then constructed based on the E2F-related prognostic genes. Evidence supported the E2F score as an independent and effective prognostic factor and predictor of immunotherapy response. A gene-set analysis correlated E2F score with the characteristics of immune cell infiltration within the TME. The immunotherapy cohort database showed that patients with a higher E2F score demonstrated better survival and immune responses.

Conclusions

This study found that differences in GC prognosis might be related to the E2F patterns in the TME. The E2F scoring system developed in this study has practical value as a predictor of survival and treatment response in GC patients.
Immobilization of 2,5‐dimethyl‐4‐benzoyl‐oxypiperidine succinate over polyacrylic acid (PAA) gels. I. Study of interaction between linear and network PAA with succinate of 2,5‐dimethyl‐4‐benzoyl‐oxypiperidine
Authors: Zhumagalieva Sh. N. , Beisebekov M. K. , Abilov Zh. A.
Published: March 2005

The interaction of water‐soluble and crosslinked polyacrylic acid (PAA) with a medicinal compound (MC) of 2,5‐dimethyl‐4‐benzoyl‐oxypiperidine succinate was investigated. By methods of potentiometry, viscosimetry, and equilibrium swelling it was confirmed that the interaction of linear and network PAA with MC proceeds with complex formation. The degree of complex formation depends on the effect of pH, MC concentration, and degree of polyacid crosslinking. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 1183–1186, 2005
Outsourcing relationships between firms and their training providers: The role of trust
Authors: Gainey Thomas W. , Klaas Brian S.
Published: March 2005

Firms increasingly use external vendors to provide training for their employees. And because trust has been found to be essential in successful interfirm relationships, this study identified a number of factors thought to be associated with both self‐interested trust and socially oriented trust between firms and their training suppliers. Using data obtained from 323 organizations, regression analysis suggests that idiosyncratic training, program uncertainty, vendor dependency, contractual specificity, and communication accuracy and frequency were significantly related to higher levels of trust in outsourcing relationships.
Work design theory: A review and critique with implications for human resource development
Authors: Torraco Richard J.
Published: March 2005

Six theoretical perspectives on work design are examined for their contributions to our understanding of how work is organized and designed in organizations: sociotechnical systems theory, process improvement, adaptive structuration theory, the job characteristics model, technostructural change models, and activity theory. A critique of these theories raises concerns about their ability to explain the design of work in new work environments. The critique highlights the need to eliminate the discontinuity in how theory explains the structure and articulation of work among system levels. The implications of this study for further research on work design theory and for human resource development practice are discussed.
A sparse algorithm for the evaluation of the local energy in quantum Monte Carlo
Authors: Aspuru‐Guzik Alán , Salomón‐Ferrer Romelia , Austin Brian , Lester William A.
Published: March 2005

A new algorithm is presented for the sparse representation and evaluation of Slater determinants in the quantum Monte Carlo (QMC) method. The approach, combined with the use of localized orbitals in a Slater‐type orbital basis set, significantly extends the size molecule that can be treated with the QMC method. Application of the algorithm to systems containing up to 390 electrons confirms that the cost of evaluating the Slater determinant scales linearly with system size. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 708–715, 2005
Cerebral blood flow measurement without absolute input function value for PET O‐15 injection method
Authors: Matsuda Tadashige
Published: March 2005

This paper presents a method of regional cerebral blood flow (CBF) measurement using PET data and an input function not involving the absolute concentration value of radioactivity. The value of the input function and the output function can be obtained from clinical data by regression analysis. The input and output functions are transformed to their Fourier image functions by the Fourier transform. The transfer function of the differential equation of a compartment model is obtained from these image functions. The CBF can be estimated by transfer function regression analysis. The results of the proposed and conventional methods are compared. © 2005 Wiley Periodicals, Inc. Syst Comp Jpn, 36(4): 20–26, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.20160