Search

Abstract The extraction of gold from refractory gold mineral deposits is becoming increasingly necessary. The presence of gold encapsulated within the crystalline matrix of iron sulfide minerals, such as pyrite, pyrrhotite, and arsenopyrite significantly reduces the efficiency of cyanidation. Therefore, the use of oxidative pretreatments, such as calcination, pressure oxidation, or bacterial leaching, enables a high gold recovery from refractory deposits. Calcination has been widely employed. However, it has a high energy cost and environmental issues due to the release of toxic gases containing arsenic. In the treatment of refractory gold ores containing arsenic, pressure oxidation (POX) represents an attractive approach for arsenic immobilization, since the conditions are suitable for both sulfide oxidation and the formation of stable arsenates. In the present study, tests of alkaline and acidic pressure oxidation followed by sodium cyanide leaching were conducted on a composite sample of the Faina Project, owned by Jaguar Mining Inc., located in de northwest portion of the Iron Quadrangle, Minas Gerais, Brazil. The mineralization is hosted by metabasalts and komatiitics metabasalts of an archean metavulcano sedimentary sequence, in the Greenstonebelt Pitangui. The tests demonstrated that it is possible to achieve a 98.40% gold recovery using a concentrate initially containing 12% sulfur, which underwent acidic oxidation with a 0.28 M H2SO4 solution at a temperature of 220°C, oxygen pressure of 500 kPa, and a residence time of three hours. This result was 19.19% higher than that obtained in an alkaline medium using a 3.0 M NaOH solution.

This paper proposes novel designs of line-of-sight multiple-input multiple-output (LOS-MIMO) and a unique sample-level coding scheme for wireless fronthaul (WFH) deployment in Open Radio Access Network (O-RAN) and beyond the fifth-generation (5G) systems. The objective of these designs is to achieve high capacity, robustness, and ultra-reliability in WFH, providing performance comparable to fiber-optic fronthaul solutions. Firstly, by optimizing array configuration parameters, such as array aperture size, antenna separation, and the proposed analog multipath beamforming scheme, LOS-MIMO operating at millimeter-wave (mmWave) bands emerges as a critical enabler for WFH, delivering the required high data rates to support lower-level split options as defined by the 3rd Generation Partnership Project for fronthaul networks. Furthermore, the use of a non-uniform array design effectively enhances the robustness of WFH by addressing the performance degradation caused by spatial aliasing when LOS-MIMO is employed with uniformly spaced linear array at shorter distances. Additionally, the proposed augmented sample-level coding not only seamlessly integrates with the fronthaul design but also provides benefits for ultra-reliable applications carried over the fronthaul. Through extensive simulations at both system and link levels, it is demonstrated that employing high-rank LOS-MIMO at mmWave bands for WFH ensures high capacity, robustness, and reliable performance. Overall, the analysis presented in this paper establishes that WFH can be effectively designed to meet the stringent requirements of fronthaul networks and represents an attractive option for future disaggregated RAN deployments.

Training deep learning models for object detection usually requires a large amount of data, a condition that is not common for most real-world applications, especially in the context of aerial imagery. One possible solution is the use of simulators to generate synthetic data. For a good generalization, the model must be able to learn on the simulated data and perform correctly on the real data, process known as sim-to-real transfer. In this work, we analyze the generation of synthetic data to account for a data-scarce real-world scenario, which includes aerial imagery and object detection of transmission towers and their components. We evaluate the impact of image-to-image translation methods as domain adaptation techniques. In this analysis, we explore training strategies to mitigate the domain shift between synthetic and real data. According to our experimental results, the use of domain-adapted data through image-to-image translation could slightly improve the detection performance in real test data when compared to training with raw synthetic images only or with small datasets of real data, although it was noted through a visual analysis that objects with small bounding boxes, like clamp, anchoring clamp and ball link, could be distorted or vanished by the application of image-to-image translation methods. Additionally, when only a small subset of real data is available, training with both real and synthetic data at once led to better detection results, surpassing combinations of pre-training on synthetic and fine-tuning on real data.

This animated movie presents the mechanism of macroautophagy, hereafter autophagy, by showing the molecular features of the formation of autophagosomes, the hallmark organelle of this intracellular catabolic pathway. It is based on our current knowledge and it also illustrates how autophagosomes can recognize and eliminate selected cargoes.

Archaea are key players in many critical ecological processes. In comparison to eukaryotes and bacteria, however, our understanding of both the cell biology and diversity of archaea remains limited. While archaea inhabit a wide range of environmental conditions, many species are extremophiles, surviving in extreme temperature, salt or pH conditions, making their cell biology hard to study. Recently, our understanding of archaeal cell biology has been advanced significantly by the advent of live cell imaging in extremis as well as the development of genetic tools to exogenously express fluorescent proteins in some mesophilic archaeal model systems, e.g., Haloferax volcanii. However, for most archaeal species, especially thermophilic species or emerging model systems without well characterized genetic tools, live cell imaging remains dependent on fluorescent chemical probes to label and track the dynamics of living cells. While a wide range of fluorescent stains and markers that label different components of the cell are available commercially, their use has usually been optimized for use in a small number of eukaryotic cell systems. Here we report the successes and failures of the application of membrane, DNA, S-layer and cytoplasm markers in live cell imaging of archaea, as well as the optimization of fixation and immunolabelling approaches. We have applied these markers to the thermoacidophilic archaeon Sulfolobus acidocaldarius, but expect some to work in other archaeal species. Furthermore, those procedures that failed in S. acidocaldarius may still prove useful for imaging archaea that grow at a more neutral pH and/or at a less extreme temperature.

Abstract Ca2+-activated K+ channels of intermediate conductance (IK) are frequently overexpressed in breast cancer (BC) cells, while IK channel depletion reduces BC cell proliferation and tumorigenesis. This raises the question, of whether and mechanistically how IK activity interferes with the metabolic activity and energy consumption rates, which are fundamental for rapidly growing cells. Using BC cells obtained from MMTV-PyMT tumor-bearing mice, we show that both, glycolysis and mitochondrial ATP-production are reduced in cells derived from IK-deficient breast tumors. Loss of IK altered the sub-/cellular K+- and Ca2+- homeostasis and mitochondrial membrane potential, ultimately resulting in reduced ATP-production and metabolic activity. Consequently, we find that BC cells lacking IK upregulate AMP-activated protein kinase activity to induce autophagy compensating the glycolytic and mitochondrial energy shortage. Our results emphasize that IK by modulating cellular Ca2+- and K+-dynamics contributes to the remodeling of metabolic pathways in cancer. Thus, targeting IK channel might disturb the metabolic activity of BC cells and reduce malignancy.

Objective: This community‐engaged codesign project identified the changes needed to tailor a family resilience‐building program, the Families Tackling Tough Times Together (FT), into a community setting. Background: There is a need for low‐burden resources to help families mitigate stressful times and build resilience. Guided by Walsh's family resilience framework, FT aims to improve families' ability to cope, recover, and build resilience. Due to the success of FT during the COVID‐19 pandemic, the program is now being modified to help families in the state of Indiana. Method: Three codesign workshops were held with community service providers (CSP) and families. Participants engaged with the FT materials and discussions related to program usability and feasibility. Data were analyzed using a rapid analysis approach. Results: CSPs stated that FT program materials fit with their goals and workload. Families felt the FT program aligned with their personal needs and day‐to‐day lives. Challenges and concerns with the FT materials included activities that required additional resources or that may be intimidating for families to complete. Both CSPs and families provided helpful suggestions on how to modify the materials. Conclusion: The FT program was well received by participants and was viewed as a valuable addition to the services CSPs offer. Modifications will be made to the FT materials based on knowledge gained from the workshops. Implications: This work highlights the collaborative nature of the codesign process as well as the insights gained from participants regarding the use of the FT materials by CSPs as part of their routine service delivery with families in the community. [ABSTRACT FROM AUTHOR]

Abstract Background Retroperitoneal germ cell tumors (GCTs) are rare, commonly large tumors, often diagnosed in infancy. Complete surgical resection may pose a serious challenge as encasement of major vessels and organ displacement can lead to perioperative complications. This study aims to illustrate the surgical challenges of excising retroperitoneal GCTs. Results Nine patients were included: six patients with a teratoma, two patients with a mixed GCT with a yolk sac tumor component, and one patient with a pure yolk sac tumor. Six were males and seven were younger than 1 year of age at time of presentation. In all cases, perioperative vascular or organ-related complications occurred in one patient; this resulted in short bowel syndrome. There was no recurrence or mortality during the follow-up period. Relevant literature is reviewed and described. Conclusions The anatomical relation of a retroperitoneal GCT to the major vessels and organs is unpredictable. Preoperative radiological evaluation can help to improve the understanding of the vascular anatomy and to plan accordingly. Anteriorly displaced veins may appear insignificant and arteries, such as the superior mesenteric artery may be encased. Preoperative imaging may prevent perioperative complications, leading to safer surgical procedures. Level IV evidence Therapeutic study

Objective: To evaluate outcomes after primary surgery (PS) or neoadjuvant treatment followed by surgery (NAT/S) in cT2 staged adenocarcinomas of the esophagus (EAC) and gastroesophageal junction (GEJ), a multinational high-volume center study was undertaken. Background: The optimal treatment approach with either NAT/S or PS for clinically staged cT2cNany or cT2N0 EAC and GEJ remains unknown due to the lack of randomized controlled trials. Methods: A retrospective analysis of prospectively maintained databases from 10 centers was performed. Between January 2012 and August 2023, 645 patients who fulfilled inclusion criteria of GEJ Siewert type I, II, or EAC with cT2 status at diagnosis underwent PS or NAT/S with curative intent. The primary endpoint was overall survival (OS). Results: In the cT2cNany cohort, 192 patients (29.8%) underwent PS and 453 (70.2%) underwentNAT/S. In all cT2cN0 patients (n = 333),NAT/s remained the more frequent treatment (56.2%). Patients undergoing PS were in both cT2 cohorts older (P < 0.001) and had a higher American Society of Anesthesiologists classification (P < 0.05). R0 resection showed no differences between NAT/S and PS in both cT2 cohorts (P > 0.4).Median OS was 51.0 months in the PS group (95% CI: 31.6--70.4) versus 114.0 months (95% CI: 53.9--174.1) in the NAT/S group (P = 0.003) of cT2cNany patients. For cT2cN0 patients,NAT/S was associated with longer OS (P = 0.002) and disease-free survival (P = 0.001). After propensity score matching of the cT2N0 patients, survival benefit for NAT/S remained (P = 0.004). Histopathology showed that 38.1% of cT2cNany and 34.2% of cT2cN0 patients were understaged. Conclusions: Due to the unreliable identification of cT2N0 disease, all patients should be offered a multimodal therapeutic approach. [ABSTRACT FROM AUTHOR]

We report a scalable hydrogenation method for nitriles based on cost-effective materials in a very simple two-electrode setup under galvanostatic conditions. All components are commercially and readily available. The method is very easy to conduct and applicable to a variety of nitrile substrates, leading exclusively to primary amine products in yields of up to 89% using an easy work-up protocol. Importantly, this method is readily transferable from the milligram scale in batch-type screening cells to the multi-gram scale in a flow-type electrolyser. The transfer to flow electrolysis enabled us to achieve a notable 20 g day−1 productivity of phenylethylamine at a geometric current density of 50 mA cm−2 in a flow-type electrolyser with 48 cm2 electrodes. It is noteworthy that this method is sustainable in terms of process safety and reusability of components. [ABSTRACT FROM AUTHOR]

Since first identified as a separate domain of life in the 1970s, it has become clear that archaea differ profoundly from both eukaryotes and bacteria. In this review, we look across the archaeal domain and discuss the diverse mechanisms by which archaea control cell cycle progression, DNA replication, and cell division. While the molecular and cellular processes archaea use to govern these critical cell biological processes often differ markedly from those described in bacteria and eukaryotes, there are also striking similarities that highlight both unique and common principles of cell cycle control across the different domains of life. Since much of the eukaryotic cell cycle machinery has its origins in archaea, exploration of the mechanisms of archaeal cell division also promises to illuminate the evolution of the eukaryotic cell cycle. [ABSTRACT FROM AUTHOR]

Aim: This study reports surgical treatment and its outcome for boys with a testicular tumor, in order to analyze the considerations of testis-sparing surgery (TSS) and investigate whether, in retrospect, treatment was according to a recently developed algorithm. Methods: We retrospectively reviewed boys with testicular tumors who underwent surgical treatment between January 2000 and June 2020 at the Wilhelmina’s Children’s Hospital and the Princess Máxima Center for Pediatric Oncology, The Netherlands. Medical records were searched for clinical characteristics and outcome. Results: We identified 31 boys (median age = 5.5 years) with a testicular tumor, 26 germ cell tumors (GCTs), four sex cord-stromal tumors, and one gonadoblastoma. Seventeen boys (median age = 1.5 years) had malignant and 14 (median age = 3.6 years) had benign tumors. Four boys with benign GCTs were treated with TSS, 25 with radical inguinal orchiectomy (RIO), and 2 with scrotal orchiectomy. No recurrence or testicular atrophy was reported. All boys with benign testicular tumors were treated as suggested by the algorithm, except for one boy treated with RIO. Conclusion: Retrospective analysis of surgical treatment of prepubertal boys with benign testicular tumors showed that TSS appears to be safe, and should be considered based on clinicoradiological data, in line with our algorithm.

Proteins can self-organize into spatial patterns via non-linear dynamic interactions on cellular membranes. Modelling and simulations have shown that small GTPases can generate patterns by coupling guanine nucleotide exchange factors (GEF) to effectors, generating a positive feedback of GTPase activation and membrane recruitment. Here, we reconstituted the patterning of the small GTPase Rab5 and its GEF/effector complex Rabex5/Rabaptin5 on supported lipid bilayers. We demonstrate a ‘handover’ of Rab5 from Rabex5 to Rabaptin5 upon nucleotide exchange. A minimal system consisting of Rab5, RabGDI and a complex of full length Rabex5/Rabaptin5 was necessary to pattern Rab5 into membrane domains. Rab5 patterning required a lipid membrane composition mimicking that of early endosomes, with PI(3)P enhancing membrane recruitment of Rab5 and acyl chain packing being critical for domain formation. The prevalence of GEF/effector coupling in nature suggests a possible universal system for small GTPase patterning involving both protein and lipid interactions.

Abstract Background Racial disparities exist in the care provided to advanced cancer patients. This article describes an investigation designed to advance the science of healthcare disparities by isolating the effects of patient race and patient activation on physician behavior using novel standardized patient (SP) methodology. Methods/design The Social and Behavioral Influences (SBI) Study is a National Cancer Institute sponsored trial conducted in Western New York State, Northern/Central Indiana, and lower Michigan. The trial uses an incomplete randomized block design, randomizing physicians to see patients who are either black or white and who are “typical” or “activated” (e.g., ask questions, express opinions, ask for clarification, etc.). The study will enroll 91 physicians. Discussion The SBI study addresses important gaps in our knowledge about racial disparities and methods to reduce them in patients with advanced cancer by using standardized patient methodology. This study is innovative in aims, design, and methodology and will point the way to interventions that can reduce racial disparities and discrimination and draw links between implicit attitudes and physician behaviors. Trial registration https://clinicaltrials.gov/ , #NCT01501006, November 30, 2011.

During autophagy, AMPK and mTOR associate with ULK1 and regulate phosphatidylinositol 3-phosphate (PtdIns3P) production that mediates autophagosome formation via WIPI proteins. Here the authors show WIPI3 and WIPI4 have a scaffolding function upstream of PtdIns3P production and have a role in the PtdIns3P effector function of WIPI1-WIPI2 at nascent autophagosomes.

Intracellular trafficking depends on the function of Rab GTPases, whose activation is regulated by guanine exchange factors (GEFs). The Rab5 GEF, Rabex5, was previously proposed to be auto-inhibited by its C-terminus. Here, we studied full-length Rabex5 and Rabaptin5 proteins as well as domain deletion Rabex5 mutants using hydrogen deuterium exchange mass spectrometry. We generated a structural model of Rabex5, using chemical cross-linking mass spectrometry and integrative modeling techniques. By correlating structural changes with nucleotide exchange activity for each construct, we uncovered new auto-regulatory roles for the ubiquitin binding domains and the Linker connecting those domains to the catalytic core of Rabex5. We further provide evidence that enhanced dynamics in the catalytic core are linked to catalysis. Our results suggest a more complex auto-regulation mechanism than previously thought and imply that ubiquitin binding serves not only to position Rabex5 but to also control its Rab5 GEF activity through allosteric structural alterations.

This article discusses the history and significance of autophagy, a cellular process that involves the degradation and recycling of intracellular material. The discovery of autophagy genes in yeast by Yoshinori Ohsumi 30 years ago paved the way for a surge of research in this field. The article highlights various aspects of autophagy, including its molecular mechanisms, regulation, and its role in human diseases such as cancer and neurodegeneration. The authors also raise important questions about the therapeutic potential of modulating autophagy and the future directions of autophagy research. [Extracted from the article]

The four human WIPI β‐propellers, WIPI1 through WIPI4, belong to the ancient PROPPIN family and fulfill scaffold functions in the control of autophagy. In this context, WIPI β‐propellers function as PI3P effectors during autophagosome formation and loss of WIPI function negatively impacts autophagy and contributes to neurodegeneration. Of particular interest are mutations in WDR45, the human gene that encodes WIPI4. Sporadic WDR45 mutations are the cause of a rare human neurodegenerative disease called BPAN, hallmarked by high brain iron accumulation. Here, we discuss the current understanding of the functions of human WIPI β‐propellers and address unanswered questions with a particular focus on the role of WIPI4 in autophagy and BPAN. [ABSTRACT FROM AUTHOR]

Autophagy is a lysosomal degradation process for cytoplasmic components, including organelles, membranes, and proteins, and critically secures eukaryotic cellular homeostasis and survival. Moreover, autophagy-related (ATG) genes are considered essential for longevity control in model organisms. Central to the regulatory relationship between autophagy and longevity is the control of insulin/insulin-like growth factor receptor-driven activation of mTOR (mechanistic target of rapamycin), which inhibits WIPI (WD repeat protein interacting with phosphoinositides)-mediated autophagosome formation. Release of the inhibitory mTOR action on autophagy permits the production of PI3P (phosphatidylinositol-3 phosphate), predominantly at the endoplasmic reticulum, to function as an initiation signal for the formation of autophagosomes. WIPI proteins detect this pool of newly produced PI3P and function as essential PI3P effector proteins that recruit downstream autophagy-related (ATG) proteins. The important role of WIPI proteins in autophagy is highlighted by functional knockout of the WIPI homologues ATG-18 and EPG-6 in Caenorhabditis elegans (C. elegans). Adult lifespan is significantly reduced in ATG-18 mutant animals, demonstrating that longevity as such is crucially determined by essential autophagy factors. In this review we summarize the role of WIPI proteins and their C. elegans homologues with regard to the molecular basis of aging. As the development of strategies on how to increase health span in humans is increasingly appreciated, we speculate that targeting WIPI protein function might represent a therapeutic opportunity to fight and delay the onset of age-related human diseases.

Archaea are key players in many critical ecological processes. In comparison to eukaryotes and bacteria, however, our understanding of both the cell biology and diversity of archaea remains limited. While archaea inhabit a wide range of environmental conditions, many species are extremophiles, surviving in extreme temperature, salt or pH conditions, making their cell biology hard to study. Recently, our understanding of archaeal cell biology has been advanced significantly by the advent of live cell imaging in extremis as well as the development of genetic tools to exogenously express fluorescent proteins in some mesophilic archaeal model systems, e.g., Haloferax volcanii. However, for most archaeal species, especially thermophilic species or emerging model systems without well characterized genetic tools, live cell imaging remains dependent on fluorescent chemical probes to label and track the dynamics of living cells. While a wide range of fluorescent stains and markers that label different components of the cell are available commercially, their use has usually been optimized for use in a small number of eukaryotic cell systems. Here we report the successes and failures of the application of membrane, DNA, S-layer and cytoplasm markers in live cell imaging of archaea, as well as the optimization of fixation and immunolabelling approaches. We have applied these markers to the thermoacidophilic archaeon Sulfolobus acidocaldarius, but expect some to work in other archaeal species. Furthermore, those procedures that failed in S. acidocaldarius may still prove useful for imaging archaea that grow at a more neutral pH and/or at a less extreme temperature. [ABSTRACT FROM AUTHOR]

During macroautophagy, the human WIPI (WD-repeat protein interacting with phosphoinositides) proteins (WIPI1–4) function as phosphatidylinositol 3-phosphate effectors at the nascent autophagosome. Likewise, the two WIPI homologues in Caenorhabditis elegans, ATG-18 and EPG-6, play important roles in autophagy, whereby ATG-18 is considered to act upstream of EPG-6 at the onset of autophagy. Due to its essential role in autophagy, ATG-18 was found to be also essential for lifespan extension in Caenorhabditis elegans; however, this has not yet been addressed with regard to EPG-6. Here, we wished to address this point and generated mutant strains that expressed the autophagy marker GFP::LGG-1 (GFP-LC3 in mammals) and harbored functional deletions of either atg-18 (atg18(gk378)), epg-6 (epg-6(bp242)) or both (atg-18(gk378);epg-6(bp242)). Using quantitative fluorescence microscopy, Western blotting, and lifespan assessments, we provide evidence that in the absence of either ATG-18 or EPG-6 autophagy was impaired, and while atg-18 mutant animals showed a short-lived phenotype, lifespan was significantly increased in epg-6 mutant animals. We speculate that the long-lived phenotype of epg-6 mutant animals points towards an autophagy-independent function of EPG-6 in lifespan control that warrants further mechanistic investigations in future studies.