Early Appearance Research Articles

Cholesterol-Lowering Therapy in Patients at Low-to-Moderate Cardiovascular Risk.

Elevated low-density lipoprotein cholesterol (LDL-C) is unanimously recognized as a major modifiable risk factor related to the development of atherosclerotic cardiovascular disease (ASCVD). Consistent evidence confirms that reducing LDL-C is associated with reduction of major adverse cardiovascular events (MACEs), with benefits proportionally related to initial individual CV risk and absolute reduction of LDL-C levels. The recent European guidelines on cardiovascular prevention have proposed a revised approach in cardiovascular risk evaluation, taking into account a renewed consideration of the interaction between risk factors and possible confounding factors (e.g., age). Although for patients considered to be at high and very high cardiovascular risk the need for stringent risk factors treatment is clearly stated, for those who are at low-to-moderate cardiovascular risk the issue is more debated. For those latter subjects, current guidelines indicate that risk factor treatment is generally not necessary, unless the impact of CV risk modifiers, lifetime CV risk and treatment benefit may be substantial. In addition, despite the estimated low-to-moderate short-term CV risk, the early appearance of even mild LDL-C level elevations may contribute to impair long-term CV prognosis. Therefore, encouraging the achievement of desired LDL-C goals through tailored conservative lifestyle changes and, if necessary, pharmacologic strategies should not be excluded categorically in all low-to-moderate risk individuals. In this review, we summarize the most recent evidence that may influence the choice to treat or not to treat LDL-C elevations in subjects at low-to-moderate risk and the suggested therapeutic tools aimed at achieving the recommended LDL-C goals.

Hypoxia promotes differentiation of human induced pluripotent stem cells into embryoid bodies in vitro

To investigate effects of physiological hypoxic conditions on suspension and adherence of embryoid bodies (EBs) during differentiation of human induced pluripotent stem cells (hiPSCs) and explore the underlying mechanisms. EBs in suspension culture were divided into normoxic (21% O2) and hypoxic (5% O2) groups, and those in adherent culture were divided into normoxic, hypoxic and hypoxia + HIF-1α inhibitor (echinomycin) groups. After characterization of the pluripotency with immunofluorescence assay, the hiPSCs were digested and suspended under normoxic and hypoxic conditions for 5 days, and the formation and morphological changes of the EBs were observed microscopically; the expressions of the markers genes of the 3 germ layers in the EBs were detected. The EBs were then inoculated into petri dishes for further culture in normoxic and hypoxic conditions for another 2 days, after which the adhesion and peripheral expansion rate of the adherent EBs were observed; the changes in the expressions of HIF-1α, β-catenin and VEGFA were detected in response to hypoxic culture and echinomycin treatment. The EBs cultured in normoxic and hypoxic conditions were all capable of differentiation into the 3 germ layers. The EBs cultured in hypoxic conditions showed reduced apoptotic debris around them with earlier appearance of cystic EBs and more uniform sizes as compared with those in normoxic culture. Hypoxic culture induced more adherent EBs than normoxic culture (P < 0.05) with also a greater outgrowth rate of the adherent EBs (P < 0.05). The EBs in hypoxic culture showed significantly up-regulated mRNA expressions of β-catenin and VEGFA (P < 0.05) and protein expressions of HIF-1 α, β-catenin and VEGFA (P < 0.05), and their protein expresisons levels were significantly lowered after treatment with echinomycin (P < 0.05). Hypoxia can promote the formation and maturation of suspended EBs and enhance their adherence and post-adherent proliferation without affecting their pluripotency for differentiation into all the 3 germ layers. Our results provide preliminary evidence that activation of HIF-1α/β-catenin/VEGFA signaling pathway can enhance the differentiation potential of hiPSCs.

Generalized Pustular Psoriasis in Pregnancy: Current and Future Treatments.

Generalized pustular psoriasis (GPP) is a rare, severe neutrophilic skin disease characterized by sudden widespread eruption of sterile pustules with or without systemic symptoms. GPP may be life threatening in cases with severe complications such as cardiovascular failure, acute respiratory distress syndrome, and serious infections. Impetigo herpetiformis (IH) is a GPP that is induced and exacerbated by pregnancy and occurs most frequently during the last trimester. IH may result in poor or fatal neonatal outcomes, including placental insufficiency, fetal abnormalities, stillbirth, and early neonatal death. Most patients have prompt remission in the postpartum period; however, earlier appearance and more severe symptoms are observed during subsequent pregnancies. Appropriate treatment and close monitoring of the mother and fetus are vital for the management of patients with IH. Particular attention is required for the management of patients with IH to avoid an influence on the fetus. However, data regarding treatments for GPP in pregnant women are sparse. Over the last decade, many patients with IH have been treated with cyclosporine, corticosteroids, tumor necrosis factor-α inhibitors, interleukin (IL)-17 and IL-12/23 inhibitors, and granulocyte and monocyte adsorption apheresis (GMA). GMA may be an important option for patients with IH as it is presently one of the safest available therapeutic options, but there have been no reports to fully confirm its safety in pregnant patients with GPP. Alternatively, based on recent advances in the understanding of the role of the IL-36 axis in the pathogenesis of GPP, biologic agents that target the IL-36 pathway may demonstrate promising efficacy in IH.

Toward RNA Life on Early Earth: From Atmospheric HCN to Biomolecule Production in Warm Little Ponds

The origin of life on Earth involves the early appearance of an information-containing molecule such as RNA. The basic building blocks of RNA could have been delivered by carbon-rich meteorites or produced in situ by processes beginning with the synthesis of hydrogen cyanide (HCN) in the early Earth’s atmosphere. Here, we construct a robust physical and nonequilibrium chemical model of the early Earth’s atmosphere. The atmosphere is supplied with hydrogen from impact degassing of meteorites, water evaporated from the oceans, carbon dioxide from volcanoes, and methane from undersea hydrothermal vents, and in it lightning and external UV-driven chemistry produce HCN. This allows us to calculate the rain-out of HCN into warm little ponds (WLPs). We then use a comprehensive numerical model of sources and sinks to compute the resulting abundances of nucleobases, ribose, and nucleotide precursors such as 2-aminooxazole resulting from aqueous and UV-driven chemistry within them. We find that 4.4 billion years ago the limit of adenine concentrations in ponds for habitable surfaces is 0.05 μM in the absence of seepage. Meteorite delivery of adenine to WLPs can provide boosts in concentration by 2–3 orders of magnitude, but these boosts deplete within months by UV photodissociation, seepage, and hydrolysis. The early evolution of the atmosphere is dominated by the decrease in hydrogen due to falling impact rates and atmospheric escape, and the rise of oxygenated species such as OH from H2O photolysis. The source of HCN is predominantly from UV radiation rather than lightning. Our work points to an early origin of RNA on Earth within ∼200 Myr of the Moon-forming impact.

The "Primitive Brain Dysfunction" Theory of Autism: The Superior Colliculus Role.

A better understanding of the pathogenesis of autism will help clarify our conception of the complexity of normal brain development. The crucial deficit may lie in the postnatal changes that vision produces in the brainstem nuclei during early life. The superior colliculus is the primary brainstem visual center. Although difficult to examine in humans with present techniques, it is known to support behaviors essential for every vertebrate to survive, such as the ability to pay attention to relevant stimuli and to produce automatic motor responses based on sensory input. From birth to death, it acts as a brain sentinel that influences basic aspects of our behavior. It is the main brainstem hub that lies between the environment and the rest of the higher neural system, making continuous, implicit decisions about where to direct our attention. The conserved cortex-like organization of the superior colliculus in all vertebrates allows the early appearance of primitive emotionally-related behaviors essential for survival. It contains first-line specialized neurons enabling the detection and tracking of faces and movements from birth. During development, it also sends the appropriate impulses to help shape brain areas necessary for social-communicative abilities. These abilities require the analysis of numerous variables, such as the simultaneous evaluation of incoming information sustained by separate brain networks (visual, auditory and sensory-motor, social, emotional, etc.), and predictive capabilities which compare present events to previous experiences and possible responses. These critical aspects of decision-making allow us to evaluate the impact that our response or behavior may provoke in others. The purpose of this review is to show that several enigmas about the complexity of autism might be explained by disruptions of collicular and brainstem functions. The results of two separate lines of investigation: 1. the cognitive, etiologic, and pathogenic aspects of autism on one hand, and two. the functional anatomy of the colliculus on the other, are considered in order to bridge the gap between basic brain science and clinical studies and to promote future research in this unexplored area.

​Phoma Blight of Soybean in Kashmir: Etiology, Relative Yield Losses and Critical Stage of Management Intervention

Background: Soybean leaf blight has been viewed as a possible biotic stress responsible for decreasing yield potential of soybean in Kashmir over the years. Therefore, its etiology and recording associated yield loss were deemed necessary corresponding to baseline findings for deciding any chemical or non-chemical intervention in disease management. Methods: Field and laboratory investigations were undertaken during crop periods of 2019 and 2020. Disease specimens were collected from various locations across valley and the pathogen was isolated on Potato Dextrose Agar medium. To identify the host range of soybean isolate, nine pulse crops were tested under controlled conditions (Tem. 22±3°C and RH greater than 80%). The relative yield loss and critical stage of chemical intervention were assessed by exposing soybean populations to disease at different phenological stages which created five different levels of disease in a field experiment laid in RBD with four replications. Result: Phoma sojicola (syn. Ascochyta sojicola) was associated pathogen of this disease of soybean in Kashmir. Typical disease symptoms on leaves comprised of roughly circular and brown lesions (up to 20 mm diameter) with concentric rings having interspersed pycnidia. Most often the diseased tissue fall apart and gives it a shot hole expression. Radial daily mycelial growth of the pathogen was 3.62 mm colony was grey olivaceous in the centre and light olivaceous towards periphery. Conidia were hyaline, oblong to ellipsoidal and 1-2 celled with average dimensions of 7.98 x 2.87 µ. Chlamydospores were brown olivaceous, globose to sub-globose with average dimensions of 16.89 x 9.30 µ. After artificial inoculation, Phaseolus vulgaris, Vigna sinensis, V. radiata, V. mungo, Cicer arietinum, Vicia faba and Cajanus cajan manifested disease symptoms after variable incubation periods of 8-13 days, while as Lens esculenta and Pisum sativum resisted the invasion. Early appearance of the Phoma blight (V-1 stage) in soybean can reach a terminal intensity of 67.16 per cent besides causing 51.72 per cent yield loss. Tolerable yield loss (5.63%) was achieved only when the crop was maintained disease free up to R-3 (beginning pod development) stage.

Acro-callous syndrome: A case report.

A malformative syndrome of unknown prevalence, the diagnosis is based on morphological ultrasound and magnetic resonance imaging of the fetus. The transmission is genetic and autosomal recessive. Courtnes has established 4 diagnostic criteria to affirm the acrocal syndrome and to eliminate the amalgam with other polymalformative syndrome.

Plasma α-Actin as an Early Marker of Muscle Damage After Repeated Bouts of Eccentric Cycling

ABSTRACT Purpose: This study aimed to examine the changes in skeletal muscle (SM) α-actin, myoglobin (Mb) and hydroxyproline (HP) in plasma and other indirect markers of muscle damage after repeated bouts of eccentric cycling. Methods: Ten healthy men (23.3 ± 2.8 years) performed two 30-min eccentric cycling bouts at 100% of maximal concentric power output (230.7 ± 36.9 W) separated by 2 weeks (ECC1 and ECC2). Maximal voluntary isometric contraction (MVIC) peak force of the knee extensor muscles, muscle soreness (SOR), pain pressure threshold (PPT) and plasma levels of SM α-actin, Mb, and HP were measured before, 0.5, 3, 24–168 h after each cycling bout. Results: MVIC peak force decreased on average 10.7 ± 13.1% more after ECC1 than ECC2. SOR was 80% greater and PPT was 12–14% lower after ECC1 than ECC2. Plasma SM α-actin levels increased at 0.5, 3, and 24–72 h after ECC1 (26.1–47.9%), and SM α-actin levels at 24 h after ECC1 were associated with muscle strength loss (r = −0.56, P = .04) and SOR (r = 0.88, P = .001). Mb levels increased at 0.5, 3, and 24 h after ECC1 (200–502%). However, Mb levels at 24 h after ECC1were not associated with muscle strength loss and SOR. HP levels remained unchanged after ECC1. ECC2 did not increase SM α-actin, Mb and HP levels. Conclusion: Our results indicate that α-actin could be used as a potential marker for the early identification of SM damage due to its early appearance in plasma and its association with other indirect markers of muscle damage.

Autistic-like behavioral effects of prenatal stress in juvenile Fmr1 mice: the relevance of sex differences and gene–environment interactions

Fragile X Syndrome (FXS) is the most common heritable form of mental retardation and monogenic cause of autism spectrum disorder (ASD). FXS is due to a mutation in the X-linked FMR1 gene and is characterized by motor, cognitive and social alterations, mostly overlapping with ASD behavioral phenotypes. The severity of these symptoms and their timing may be exacerbated and/or advanced by environmental adversity interacting with the genetic mutation. We therefore tested the effects of the prenatal exposure to unpredictable chronic stress on the behavioral phenotype of juveniles of both sexes in the Fmr1 knock-out (KO) mouse model of FXS. Mice underwent behavioral tests at 7–8 weeks of age, that is, when most of the relevant behavioral alterations are absent or mild in Fmr1-KOs. Stress induced the early appearance of deficits in spontaneous alternation in KO male mice, without exacerbating the behavioral phenotype of mutant females. In males stress also altered social interaction and communication, but mostly in WT mice, while in females it induced effects on locomotion and communication in mice of both genotypes. Our data therefore highlight the sex-dependent relevance of early environmental stressors to interact with genetic factors to influence the appearance of selected FXS- and ASD-like phenotypes.

Cellular Senescence as Fibrogenic Mechanism in Smoking Lung

Age is a risk factor for many diseases including idiopathic pulmonary fibrosis (IPF) by affecting wound healing through abnormal fibrogenesis. Common cellular and molecular traits associated with aging can be found in senescent cells, which may occur throughout the lifespan playing physiological roles during normal development or limiting the proliferation of damaged and aged cells. In this study we investigated in smoking mice whether the senescence of lung cells, triggered by the oxidative stress response, is associated with molecular pathways that can influence lung fibrogenesis and contribute to the remodeling of the fibrotic tissue characterizing some phenotypes of COPD in humans. Among the complex mixture of hundreds senescence secreted factors that include proinflammatory cytokines, chemokines, growth factors, and proteases, we selected important factors involved in differentiation of myofibroblasts, their dedifferentiation and apoptosis, as well as in their metabolic function.The expression of these factors and the amount of matrix deposition was analyzed after chronic cigarette smoke (CS) exposure of C57 Bl/6 and DBA/2 mice sensitive to oxidative, in different lung compartmentscharacterized by a fibrotic remodeling using histochemistry or immunohistochemistry.Unlike C57 Bl/6, DBA/2 mice at 4 months of exposure show marked positivity for 8‐OHdG, a marker of oxidative damage, in subpleural areas, in central parts of the lung parenchyma, on airways and on cells of the fibro‐muscular layer.In these areas, a marked positivity is observed for fibrogenic cytokines such as TGF‐β, PDGF‐b and CTGF, and for other factors such as the p16ink4A senescence marker, and proliferation markers PCNA and Ki67. In DBA/2 mice, these compartments are characterized by a progressive fibrous remodeling at various experimental time points from 5 months of CS exposure onwards as demonstrated by Masson’s trichrome staining.Fibroproliferative foci are present in sub‐pleural areas, in peripheral areas of airways, and in central parts of the lung parenchyma. They are characterized by increasing number of α‐SMA positive myofibroblasts, which express the senescence marker p16ink4A and the transcription factor MyoD that plays a crucial role in myoblast proliferation and differentiation. MyoD induces cell cycle arrest, promotes cellular terminal differentiation of fibroblasts into myofibroblasts, and in senescent myofibroblasts it has been reported to determine resistance to apoptosis and opposes their dedifferentiation.All these factors contribute to the development in smoking DBA/2 mice of lung lesions, which are like those seen in patients with “Combined Fibrosis/Emphysema Syndrome.”Despite consistent levels of TGF‐β, PDGF‐b and CTGF, C57 Bl/6 mice develop after chronic CS exposure fibrotic remodeling at lower extent. Of interest, a very low expression of factors indicative of senescence (p16ink4A and MyoD) and cell proliferation (PCNA and Ki67) is observed.Our results suggest that apoptosis, senescence, and proliferation induced at different rate by fibrotic cytokines and senescence associated secretory factors play important role in early or late appearance of fibrotic remodeling of lung and airways exposed to CS.

Effects of primary air velocity on co-combustion characteristics of bituminous coal and semicoke under reducing-to-oxidizing environment

This study evaluated the effect of primary air velocity (PAV) on the ignition characteristics of bituminous coal and semicoke mixture (1:1, wt%) in a reducing-to-oxidizing environment (R-O) in a 300-kW pilot-scale furnace that characterized the ignition behaviors of pulverized coal (PC) furnaces. The early ignition characteristics of the primary combustion zone (PCZ), including ignition distance, ignition mode, flame stability and kinetic parameters, were studied. The results showed that the difference in ignition delays obtained from the flame temperature and O2 profiles indicated that convection heating was more important than radiant heating for fuel ignition. The transformation of the ignition mode from non-homogeneous to homogeneous with the increase in PAV was confirmed by the changes of flame temperature, residues, and flue gas composition. Flame stability was optimized by the earlier appearance of the continuous flame boundary and was the best at a PAV of 18 m/s. A simplified first-order kinetic model based on the CO2 evolution profile was established to calculate the reaction rate of the blended fuel during ignition, and the experimental char burnout ratio was consistent with the predicted result. For the potential application of co-firing bituminous coal with a large proportion of semicoke, the recommended PAV may be no more than 22 m/s.

Spontaneous Activity In Abductor Digiti Minimi )Adm( As An Early Indicator Of The Irritation Of The Ulnar Nerve At The Elbow Joint

The cubital tunnel syndrome (CuTS) is a neurological disorder that affects the ulnar nerve as it passes through the elbow joint. It may induce several physical disabilities in the affected person. The early manifestation of CuTS maybe not be well recognized clearly. The abductor digiti minimi (sometimes abductor digiti quinti, ADM) muscle is located on the ulnar side of the palm in human anatomy. The study aims to evaluate the feasibility of using the early appearance of spontaneous activity in ADM as a predictor of ulnar nerve irritation at the elbow joint. Patients and method: 67 patients were included in the study, and all of them complained of neurological manifestations. A short segment study for the ulnar nerve at the elbow joint and the Guyon`s canal was done. In addition, needle EMG was done for the ulnar innervated muscles below the level of the elbow joint, including first dorsal interossii (FDI) and abductor digiti minimi (ADM) muscles. Results: 18 of them show normal NCS of the ulnar nerve. 10 show spontaneous activity by needle EMG in the ADM only, and 9 show normal needle EMG. Conclusion: the presence of spontaneous activity in the ADM muscle may be the early signs of electrodiagnosis of cubital tunnel syndrome.

Spontaneous Activity In Abductor Digiti Minimi )Adm( As An Early Indicator Of The Irritation Of The Ulnar Nerve At The Elbow Joint

The cubital tunnel syndrome (CuTS) is a neurological disorder that affects the ulnar nerve as it passes through the elbow joint. It may induce several physical disabilities in the affected person. The early manifestation of CuTS maybe not be well recognized clearly. The abductor digiti minimi (sometimes abductor digiti quinti, ADM) muscle is located on the ulnar side of the palm in human anatomy. The study aims to evaluate the feasibility of using the early appearance of spontaneous activity in ADM as a predictor of ulnar nerve irritation at the elbow joint. Patients and method: 67 patients were included in the study, and all of them complained of neurological manifestations. A short segment study for the ulnar nerve at the elbow joint and the Guyon`s canal was done. In addition, needle EMG was done for the ulnar innervated muscles below the level of the elbow joint, including first dorsal interossii (FDI) and abductor digiti minimi (ADM) muscles. Results: 18 of them show normal NCS of the ulnar nerve. 10 show spontaneous activity by needle EMG in the ADM only, and 9 show normal needle EMG. Conclusion: the presence of spontaneous activity in the ADM muscle may be the early signs of electrodiagnosis of cubital tunnel syndrome.

Tracking oocyte development and the timing of skipped spawning for north-east Arctic haddock (Melanogrammus aeglefinus).

The present study tracked oocyte development over 9 months and noted incidences of ‘skipping’, i.e., adults terminating their upcoming reproductive cycle, in field‐caught north‐east Arctic (NEA) haddock (Melanogrammus aeglefinus), currently the largest stock of this species. Applications of advanced image and histological techniques revealed the presence of cortical alveoli oocytes (CAO), which prevailed as the most advanced oocyte phase for 4–5 months. This new finding of an extended and early appearance of CAOs in this gadoid was supported by that vitellogenesis first started to appear 3 months later. The subsequent oocyte growth trajectories indicated that larger individuals [total length (TL) = 70 cm] typically spawn in the order of 3 weeks earlier than the smaller ones (TL = 40 cm). The spawning season appeared stretched over about 3 months. The majority of skipping females arrested oocyte growth at the CAO phase followed by atretic reabsorption. Compared to those individuals maturing for the spawning season, ‘skippers’ generally exhibited lower body condition, characterized also by relatively lower liver sizes at the time of the main spawning season. This study demonstrated well‐developed skipping dynamics, but also that the CAO period, i.e., when skipping takes place, may be exceedingly long in this commercially valuable gadoid and that its reproductive cycle in many ways deviates from that of the data‐rich, sympatric NEA cod (Gadus morhua).

The genomic landscape of metastatic clear cell renal cell carcinoma after systemic therapy.

Primary clear cell renal cell carcinoma (ccRCC) has been previously characterized, but the genomic landscape of metastatic ccRCC is largely unexplored. Here, we performed whole exome sequencing (WES) in 68 samples from 44 patients with ccRCC, including 52 samples from a metastatic site. SETD2, PBRM1, APC and VHL were the most frequently mutated genes in the metastatic ccRCC cohort. RBM10 and FBXW7 were also among the 10 most frequently mutated genes in metastatic tissues. Recurrent somatic copy number variations (CNV) were observed at the previously identified regions 3p25, 9p21 and 14q25, but also at 6p21 (CDKN1A) and 13q14 (RB1). No statistically significant differences were found between samples from therapy‐naïve and pretreated patients. Clonal evolution analyses with multiple samples from 13 patients suggested that early appearance of CNVs at 3p25, 9p21 and 14q25 may be associated with rapid clinical progression. Overall, the genomic landscapes of primary and metastatic ccRCC seem to share frequent CNVs at 3p25, 9p21 and 14q25. Future work will clarify the implication of RBM10 and FBXW7 mutations and 6p21 and 13q14 CNVs in metastatic ccRCC.

In the Studio with Paula Rego: An Interview with Anthony Rudolf, Poet, Translator and Artist's Model

During the more than half a century since his earliest appearances in print, Anthony Rudolf has published many works in prose and verse, and also translated (and co-translated) books, mainly poetry, from the French and other languages. As a literary essayist, he has written on authors as diverse as Balzac, Byron, Borges and George Oppen, as well as several essays on Primo Levi and Yves Bonnefoy. He has also written on the work of visual artists, including Paula Rego, R. B. Kitaj, Vilhelm Hammershøi, Charlotte Salomon and Fermin Rocker, and younger artists including Haidee Becker, Jane Joseph, Jane Bustin, Arturo di Stephano, Paul Coldwell and Charlotte Hodes. In addition, he is a reviewer and obituarist and has contributed to Radio Three, Radio Four and—in English, French and Russian—the BBC World Service. Born in London in 1942, he still lives in the north-west of the city. His books include Jerzyk (2017), a study of the diary of his second cousin, the youngest known suicide of the Holocaust; Silent Conversations (2013) (a book on his reading); and European Hours (collected poems, 2017), whose eponymous prologue is a prose poem about places visited with Paula over the years.

Corrosion monitoring by open circuit potential in steel reinforcements embedded in cementitious composites with industrial wastes

Corrosion is one of the main issues affecting service life of reinforced concrete structures. The Open Circuit Potential (OCP) technique is a non-destructive method used to survey and monitor this problem. This test can also be used in laboratory environment and provide valuable information supporting the selection process of supplementary materials for durable concretes. Although this qualitative technique is commonly used, there is still a lack of consensus on the suitability of specific procedures for experimental analysis, such as type of reference electrode and influence of accelerated aging procedures (adoption of wetting/drying cycles and level of immersion of specimens). Therefore, the present study aims to evaluate the method for prediction of early steel corrosion activity in the accelerated OCP tests. The paper is focused on testing eco-efficient cementitious composites containing industrial wastes, such as sugarcane bagasse ash sand (SBAS) and water treatment plant sludge (WTPS), in replacement of natural sand. The results showed that an adoption of combined wetting/drying cycles, together with a partial (rather than total) immersion of specimens in NaCl solution, leads to earlier appearance of corrosion. This allows to shorten the period of testing by almost 10 weeks. It is due to higher access to oxygen and higher concentration of free chlorides from the saline solution accumulated in a porous system. The type of reference electrode is of lesser importance. Moreover, incorporation of 30% SBAS and 3% WTPS results in higher protection for steel corrosion, confirming wide applicability of the OCP technique to any cementitious matrices with or without industrial wastes.

Early Recurrence of Cromophobic Renal Cell Carcinoma with Sarcomatoid and Rhabdoid Differentiation: About a Case

Chromophobic renal cell carcinoma with sarcomatoid differentiation is a rare tumor characterized by a biphasic tumor with both classic epithelial components and sarcomatoid components with poor prognostic factors, usually in association with the rhabdoid contingent which has the potential to behave aggressively and metastasize. We report a particular case of recurrence of this entity in a male patient in which the diagnosis was suspicious preoperatively for the tumor evolution time and the size of the mass and the imaging data performed. The patient underwent extensive left total nephrectomy and lymph node dissection. The postoperative follow up was marked by early appearance of recurrence within 6 weeks after surgery.

Genetic code degeneracy is established by the decoding center of the ribosome.

The degeneracy of the genetic code confers a wide array of properties to coding sequences. Yet, its origin is still unclear. A structural analysis has shown that the stability of the Watson–Crick base pair at the second position of the anticodon–codon interaction is a critical parameter controlling the extent of non-specific pairings accepted at the third position by the ribosome, a flexibility at the root of degeneracy. Based on recent cryo-EM analyses, the present work shows that residue A1493 of the decoding center provides a significant contribution to the stability of this base pair, revealing that the ribosome is directly involved in the establishment of degeneracy. Building on existing evolutionary models, we show the evidence that the early appearance of A1493 and A1492 established the basis of degeneracy when an elementary kinetic scheme of translation was prevailing. Logical considerations on the expansion of this kinetic scheme indicate that the acquisition of the peptidyl transferase center was the next major evolutionary step, while the induced-fit mechanism, that enables a sharp selection of the tRNAs, necessarily arose later when G530 was acquired by the decoding center.

Lower Paleolithic Winds of Change: Prepared Core Technologies and the Onset of the Levallois Method in the Levantine Late Acheulian

The life cycle of a successful technological innovation usually follows a well-known path: a slow inception, gradual assimilation of the technology, an increase in its frequency up to a certain peak, and then a decline. These different phases are characterized not only by varying frequency of use but also by degree of standardization and distinguishability. The Levallois method, a sophisticated Middle Paleolithic technology aimed at producing desired stone items of predetermined morphology, is one such innovation. It has been repeatedly suggested that the Levallois method originated within earlier Lower Paleolithic Acheulian industries, and this work contributes to this discussion. We analyze the reduction trajectory of prepared cores and predetermined blanks from the late Acheulian sites of Jaljulia and Revadim, adding important new evidence for the Lower Paleolithic origins of the Levallois method and its adoption and assimilation in the human stone-tool repertoire of this period in the Levant. Revadim and Jaljulia also provide a rare opportunity to study patterns in the early assimilation of technological innovations. These sites yielded rich lithic assemblages typical of the late Acheulian in the Levant. The assemblages include handaxes but are mostly dominated by flake production technologies and flake-tools. The early appearance of prepared cores at both sites signals, in our view, the inception of concepts related to the Levallois method, termed here proto-Levallois, in the late Acheulian Levant. Through a detailed analysis of prepared cores and their products, we are able to characterize the early stages of assimilation of this method, using it as a case study in a broader discussion of the adoption and assimilation of technological innovations during Lower Paleolithic times.