RESUMEN
Background: Estimated pulse wave velocity (ePWV), which measures vascular aging, is an independent predictor of cardiovascular death. Nevertheless, the relationship between ePWV and all-cause mortality among patients suffering from non-traumatic subarachnoid hemorrhages (NSAH) remains obscure. Consequently, the objective of this study is to ascertain whether ePWV exerts influence on the prognosis of individuals afflicted with NSAH. Methods: Through the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, 644 eligible participants were included. The Kaplan-Meier survival curve method was employed to assess the disparity in survival status between the low and high ePWV cohorts. The Cox proportional hazard model was employed to investigate the association between ePWV and inpatient mortality among critically ill patients diagnosed with NSAH. The Restricted Cubic Spline (RCS) model was employed to examine the dose-response correlation. Subsequently, multivariate Cox regression analysis was performed to identify independent prognostic factors. Lastly, the impact of ePWV on inpatient mortality across various subgroups was evaluated through stratified analysis. Results: Participants were categorized into two groups, delineated by their ePWV levels: a low ePWV level group and a high ePWV level group. Survival analysis unveiled that individuals with high ePWV exhibited a diminished survival rate compared to their counterparts with low ePWV. Following adjustment, low ePWV was significantly linked with a reduced risk of inpatient mortality among patients with NSAH (HR = 0.54, 95% CI = 0.32-0.89, p = 0.016). Simultaneously, analysis employing the RCS model further substantiated a linear escalation in the risk of inpatient mortality with increasing ePWV values. Conclusion: Elevated ePWV levels have been identified as an independent risk factor for the rise in inpatient mortality among NSAH patients and as a significant predictor of the clinical outcome of NSAH.
RESUMEN
We previously described an in vitro single-chain fragment (scFv) library platform originally designed to generate antibodies with excellent developability properties. The platform design was based on the use of clinical antibodies as scaffolds into which replicated natural complementarity-determining regions purged of sequence liabilities were inserted, and the use of phage and yeast display to carry out antibody selection. In addition to being developable, antibodies generated using our platform were extremely diverse, with most campaigns yielding sub-nanomolar binders. Here, we describe a platform advancement that incorporates Fab phage display followed by single-chain antibody-binding fragment Fab (scFab) yeast display. The scFab single-gene format provides balanced expression of light and heavy chains, with enhanced conversion to IgG, thereby combining the advantages of scFvs and Fabs. A meticulously engineered, quality-controlled Fab phage library was created using design principles similar to those used to create the scFv library. A diverse panel of binding scFabs, with high conversion efficiency to IgG, was isolated against two targets. This study highlights the compatibility of phage and yeast display with a Fab semi-synthetic library design, offering an efficient approach to generate drug-like antibodies directly, facilitating their conversion to potential therapeutic candidates.
Asunto(s)
Afinidad de Anticuerpos , Fragmentos Fab de Inmunoglobulinas , Biblioteca de Péptidos , Anticuerpos de Cadena Única , Fragmentos Fab de Inmunoglobulinas/genética , Fragmentos Fab de Inmunoglobulinas/inmunología , Fragmentos Fab de Inmunoglobulinas/química , Humanos , Anticuerpos de Cadena Única/genética , Anticuerpos de Cadena Única/inmunología , Anticuerpos de Cadena Única/química , Afinidad de Anticuerpos/inmunología , Técnicas de Visualización de Superficie Celular/métodos , Inmunoglobulina G/genética , Inmunoglobulina G/inmunología , Inmunoglobulina G/químicaRESUMEN
Background: Antimicrobial agents' wastage is a huge problem, especially for pediatric patients, resulting in excessive drug expenditure and increasing the economic burden on patients' families. Moreover, the cost of disposing of antimicrobial agents' waste and the risk of environmental and occupational exposure also increased. This study aimed to explore the cost-effectiveness of the vial-sharing strategy combined with the daily-rate charge mode for pediatric inpatients to provide a strategy for reducing patients' expenditures, saving medical costs, and reducing drug proportion. Methods: This retrospective study was conducted at Pharmacy Intravenous Admixture Service (PIVAS), Shenzhen Children's Hospital, Guangdong Province, China, in 2022. Data on prescription drugs were collected from the PIVAS system. Ten antimicrobial drugs with a frequency of prescriptions no less than twice once daily were selected, and the drug costs, drug weight, and drug saved were further analyzed according to the combination of real-time vial sharing strategy and daily-rate charge mode. Traditional single vial charge mode without vial sharing was set as a control strategy. The actual expenditure of the hospital was also calculated and analyzed. Results: During 2022, ¥ 4,122,099 (34.4%) was saved for inpatients by applying a vial-sharing strategy on ten antibacterial agents, and more than 46,343,750 mg (24.6%) of drugs were totally saved. The top 5 drugs saved by the real-time vial-sharing strategy were cefoperazone-sulbactam, vancomycin, amoxicillin-sulbactam, ceftazidime, and meropenem. Taken the price into consideration, the top five payment-saved drugs were vancomycin (¥ 1,522,385), meropenem (¥ 1,311,475), cefoperazone-sulbactam (¥ 736,697), imipenem-cilastatin (¥ 406,092), and amoxicillin-sulbactam (¥ 51,394). Moreover, the account balance of the hospital was up to ¥ 426,499. Conclusion: The real-time vial sharing strategy combined with the daily-rate charge mode greatly reduces drug wastage and patients' payments. It may be useful for hospitals with PIVAS to achieve vial-sharing while protecting the best interest of inpatients.
RESUMEN
Thermal infrared technology is utilized for detecting mastitis in cows owing to its non-invasive and efficient characteristics. However, the presence of surrounding regions and obstacles can impede accurate temperature measurement, thereby compromising the effectiveness of dairy mastitis detection. To address these problems, we proposed the CLE-UNet (Centroid Loss Ellipticization UNet) semantic segmentation algorithm. The algorithm consists of three main parts. Firstly, we introduced the efficient channel attention (ECA) mechanism in the feature extraction layer of UNet to improve the segmentation accuracy by focusing on more useful channel features. Secondly, we proposed a new centroid loss function to facilitate the network's output to be closer to the position of the real label during the training process. Finally, we used a cow's eye ellipse fitting operation based on the similarity between the shape of the cow's eye and the ellipse. The results indicated that the CLE-UNet model obtained a mean intersection over union (MIoU) of 89.32% and an average segmentation speed of 0.049 s per frame. Compared to somatic cell count (SCC), this method achieved an accuracy, sensitivity, and F1 value of 86.67%, 82.35%, and 87.5%, respectively, for detecting mastitis in dairy cows. In conclusion, the innovative use of the CLE-UNet algorithm has significantly improved the segmentation accuracy and has proven to be an effective tool for accurately detecting cow mastitis.
RESUMEN
In this paper, we first formulate a system of ODEs-PDE to model diseases with latency-age and differential infectivity. Then, based on the ways how latent individuals leave the latent stage, one ODE and two DDE models are derived. We only focus on the global stability of the models. All the models have some similarities in the existence of equilibria. Each model has a threshold dynamics for global stability, which is completely characterized by the basic reproduction number. The approach is the Lyapunov direct method. We propose an idea on constructing Lyapunov functionals for the two DDE and the original ODEs-PDE models. During verifying the negative (semi-)definiteness of derivatives of the Lyapunov functionals along solutions, a novel positive definite function and a new inequality are used. The idea here is also helpful in applying the Lyapunov direct method to prove the global stability of some epidemic models with age structure or delays.
Asunto(s)
Epidemias , Modelos Biológicos , Humanos , Número Básico de ReproducciónRESUMEN
We propose a new, to the best of our knowledge, method of incoherent optical frequency selection called three-pack frequency-selective incoherent holography. Compressed holography is reconstructed using phase shift intercepts and spatial transfer function convolution in the form of separation without loss of magnification or resolution. The frequency-selective reconstruction process removes the conjugate and DC terms along with the interception of the object wave. This work attempts three-dimensional reconstruction and selected-frequency phase extraction of axial slices in submicron steps, and the experimental results show the potential of the proposed method in areas such as compressed holography, extended field of view, and slice tomography.
RESUMEN
RATIONALE: Paxlovid has shown the potential decreasing the hospitalization rate of mild or moderate coronavirus disease 2019 (COVID-19) and death in few of clinical trials, and is expected to the most promising medicine targeting Severe Acute Respiratory Syndrome Coronavirus 2 (SRAS-COV-2). However, there are no enough evidences to show it effectiveness for all patients with SARS-COV-2, especially among elderly patients and newest Omicron variant. PATIENT CONCERNS AND DIAGNOSIS: A 79 year's old female patient was admitted to hospital because of the moderate COVID-19 caused by the Omicron variant BA2.0. He presented the initial syndromes including Xerostomia, cough and fever. Chest computed tomography (CT) scanning at admission showed the exudation lesions on lung. The laboratory examination revealed that there are increased C-reactive protein (CRP), Ferritin and erythrocytesedimentationrate (ESR) and decreased white blood cells. INTERVENTIONS: The oral Paxlovid (Nirmatrelvir/Ritonavir) was administrated on second day after admission. OUTCOMES: The syndromes of Xerostomia, cough and fever was improved on third day after use of Paxlovid. The levels of CRP, ESR and counts of white blood cells returned the normal after three days of admission. The chest CT scanned on the third and sixth day after Paxlovid used showed the absorption of lesions. The examination of SARS-COVS viral nucleic acid turned negative at fifth day of admission. LESSONS: As a result, we would consider that Paxlovid is a suitable oral drug for elderly patients with SARS-COV2 even Omicron variant, it's benefit to improve patient's symptom and signs and can prevents COVID-19 with the high-risk factors from severe disease, although it didn't shorten the time for viral nucleic acid to turn negative.
Asunto(s)
COVID-19 , Xerostomía , Masculino , Humanos , Femenino , Anciano , SARS-CoV-2 , Tos/etiología , ARN Viral , Fiebre/etiologíaRESUMEN
With the continuous development of network communication technology, the domestic network has covered the homes of ordinary people, but the indoor coverage system of the network cable network needs to be further improved. The optical fiber distribution system is a signal coverage system integrating GSM, TD-SCDMA, and other standards. It is mainly composed of system access unit, system expansion unit, and system remote unit. Wireless network is an important communication technology, which is easy to use and can be connected wirelessly over long distances. The purpose of this paper is to study an optical fiber distribution system for indoor coverage design of wireless networks, so as to achieve faster and more efficient coverage. In this paper, a wireless network signal processing algorithm is proposed, and a systematic method for designing the wireless network indoor coverage of the optical fiber distribution system is proposed, and the algorithms are compared and tested. The test results in this paper show that the signal strength obtained by the algorithm in this paper is -54.83 dB, while the traditional artificial design algorithm is only -45.97 dB. In addition, the wireless network base point of the algorithm in this paper is also 3 lower than the traditional one. Moreover, the coverage rate achieved by the algorithm in this paper is 3.17% higher than that of the network cable network base point layout given by the genetic algorithm, and the average received signal strength is 3.34 dB higher. In addition, the algorithm in this paper takes 9.1 s, 11.2 s, and 5.3 s for the three scenarios of underground parking lot, large shopping mall, and residential residential area, while the traditional manual design algorithm takes 87.9 s, 108.8 s, and 51.7 s, respectively. The algorithm in this paper is only about 1/10 of the traditional artificial design algorithm. Therefore, it can be concluded that the coverage effect of the wireless network indoor coverage system of the optical fiber distribution system designed in this paper is significantly improved.
RESUMEN
Sustainable processes for semi-hydrogenation of alkynes/alkadienes impurities in alkenes feedstocks are in great demand in industry as the utilization of excessive hydrogen, high temperature and unsatisfactory alkenes selectivity of the current thermo-catalytic route, however, their development is still challenging. Herein, we innovate a light-assisted semi-hydrogenation process in gas-feed fixed bed reactor, with water as hydrogen atom source by in situ photocatalysis. Using Pd/TiO2 as model catalyst, this process shows an excellent catalytic performance for the semi-hydrogenation of 1,3-butadiene, with 100 % of butenes selectivity at ≈99 % of conversion over 180â h of reaction at ambient temperature driven by 66â mW cm-2 of irradiation intensity. This light-driven, H2 -free, ambient temperature semi-hydrogenation process, with superior performance to that of thermocatalytic route, shows attractive to bring an evolution in industrial hydrogenation technology to an economical and safe way.
RESUMEN
In this paper, we investigate the global dynamics of a viral infection model with defectively infected cells. The explicit expression of the basic reproduction number of virus is obtained by using the next generation matrix approach, where each term has a clear biological interpretation. We show that the basic reproduction number serves as a threshold parameter. The virus dies out if the basic reproduction number is not greater than unity, otherwise the virus persists and the viral load eventually approaches a positive number. The result is established by Lyapunov's direct method. Our novel arguments for the stability of the infection equilibrium not only simplify the analysis (compared with some traditional ones in the literature) but also demonstrate some correlation between the two Lyapunov functions for the infection-free and infection equilibria.
Asunto(s)
Modelos Biológicos , Virosis , Número Básico de Reproducción , Humanos , Carga ViralRESUMEN
BACKGROUND: Klebsiella pneumoniae (K. pneumoniae) is an infective microorganism of worldwide concern because of its varied manifestations and life-threatening potential. Genetic analyses have revealed that subspecies of K. pneumoniae exhibit higher virulence and mortality. However, infections with Klebsiella subspecies are often misdiagnosed and underestimated in the clinic because of difficulties in distinguishing K. pneumoniae from its subspecies using routine tests. This case study reports the rapid and fatal effects of K. pneumoniae subspecies. CASE SUMMARY: A 52-year-old male patient was febrile and admitted to hospital. Examinations excluded viral and fungal causes along with mycoplasma/chlamydia and parasitic infections. Bacterial cultures revealed blood-borne K. pneumoniae sensitive to carbapenem antibiotics, although corresponding treatment failed to improve the patient's symptoms. His condition worsened and death occurred within 72 h of symptom onset from sepsis shock. Application of the PMseq-DNA Pro high throughput gene detection assay was implemented with results obtained after death showing a mixed infection of K. pneumoniae and Klebsiella variicola (K. variicola). Clinical evidence suggested that K. variicola rather than K. pneumoniae contributed to the patient's poor prognosis. CONCLUSION: This is the first case report to show patient death from Klebsiella subspecies infection within a short period of time. This case provides a timely reminder of the clinical hazards posed by Klebsiella subspecies and highlights the limitations of classical laboratory methods in guiding anti-infective therapies for complex cases. Moreover, this report serves as reference for physicians diagnosing similar diseases and provides a recommendation to employ early genetic detection to aid patient diagnosis and management.
RESUMEN
The water sensitivity of metal-organic frameworks (MOFs) as a common and crucial issue has greatly hindered their practical applications. Here, we present a facile and general approach to improve the water resistance of a typical MOF, i.e., CuBTC [Cu3(BTC)2(H2O)3]n (BTC = benzene-1,3,5-tricarboxylate) using a post-modification reaction with aminopropyltriethoxylsilane (APTES) at room temperature. The afforded material is denoted as CuBTC@APTES. Various spectroscopic methods reveal that the organosilicon linkers have been successfully grafted onto CuBTC by electrostatic attraction between acid and base groups and without affecting the original coordination mode and basic structure. Compared with CuBTC, the water stability of CuBTC@APTES was significantly improved. The pristine CuBTC almost lost all its crystallinity, morphology and pore structure after 3-day treatment in water, while CuBTC@APTES is able to retain its main crystal structure and basic porosity after the same treatment. This finding can be explained by the successful introduction of the organosilicon molecular overlayer on the periphery of CuBTC to slow down the destruction of weak metal coordination bonds by water molecules, thus improving the water stability of CuBTC. The solution of water sensitivity provides more opportunities for the practical applications of CuBTC, such as aqueous phase catalysis and gas separation in humid environments. This simple approach can certainly be expanded to improve the water resistance of other carboxylate-containing ligand-based MOFs.
RESUMEN
Herein, we present two novel ferrocene-containing porous organic polymers, FPOP-1 and FPOP-2, by the Heck reactions of 1,1'-divinylferrocene with two tetrahedral silicon-centered units, i.e., tetrakis(4-bromophenyl)silane and tetrakis(4'-bromo-[1,1'-biphenyl]-4-yl)silane. The resulting materials possess high thermal stability and moderate porosity with the Brunauer-Emmer-Teller (BET) surface areas of 499 m2 g-1 (FPOP-1) and 354 m2 g-1 (FPOP-2) and total pore volumes of 0.43 cm3 g-1 (FPOP-1) and 0.49 cm3 g-1 (FPOP-2). The porosity is comparable to previously reported ferrocene-containing porous polymers. These materials possess comparable CO2 capacities of 1.16 mmol g-1 (5.10 wt%) at 273 K and 1.0 bar, and 0.54 mmol g-1 (2.38 wt%) at 298 K and 1.0 bar (FPOP-1). The found capacities are comparable to, or higher than many porous polymers having similar or higher surface areas. They have high isosteric heats of up to 32.9 kJ mol-1, proving that the affinity between the polymer network and CO2 is high, which can be explained by the presence of ferrocene units in the porous networks. These results indicate that these materials can be promisingly utilized as candidates for the storage or capture of CO2. More ferrocene-containing porous polymers can be designed and synthesized by combining ferrocene units with various aromatic monomers under this strategy and their applications could be explored.
RESUMEN
Sepsis is an acute inflammatory reaction and a cause of acute respiratory distress syndrome (ARDS). In the present study, we explored the roles and underlying mechanism of the lncRNA Nuclear enriched abundant transcript 1 (NEAT1) in ARDS. The expression levels of genes, proteins and pro-inflammatory cytokines in patients with ARDS, LPS-stimulated cells and septic mouse models were quantified using qPCR, western blotting and ELISA assays, respectively. The molecular targeting relationship was validated by conducting a dual-luciferase reporter assay. Cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8) assay. The cell cycle phase was determined by flow cytometry assay. The expression levels of NEAT1 and pro-inflammatory cytokines were higher in patients with ARDS and septic models than in controls. Knockdown of NEAT1 significantly increased cell proliferation and cycle progression and prolonged mouse survival in vitro and in vivo. Mechanistically, miR-27a was identified as a downstream target of NEAT1 and directly inhibited PTEN expression. Further rescue experiments revealed that inhibition of miR-27a impeded the promoting effects of NEAT1 silence on cell proliferation and cycle progression, whereas inhibition of PTEN markedly weakened the inhibitory effects of NEAT1 overexpression on cell proliferation and cycle progression. Altogether, our study revealed that NEAT1 plays a promoting role in the progression of ARDS via the NEAT1/miR-27a/PTEN regulatory network, providing new insight into the pathologic mechanism behind ARDS.
Asunto(s)
MicroARNs/metabolismo , Fosfohidrolasa PTEN/metabolismo , ARN Largo no Codificante , Síndrome de Dificultad Respiratoria/metabolismo , Sepsis/metabolismo , Adulto , Animales , Línea Celular , Modelos Animales de Enfermedad , Técnicas de Silenciamiento del Gen , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , MicroARNs/genética , Fosfohidrolasa PTEN/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Transducción de Señal/genéticaRESUMEN
BACKGROUND: A disease caused by a novel coronavirus virus, named coronavirus disease 2019 (COVID-19), broke out in Wuhan, China in December 2019, and spread around the word. As of March 4, 2020, 93090 confirmed cases and 2984 deaths have been reported in more than 80 countries and territories. It has triggered global public health security. However, the features and prognosis of COVID-19 are incompletely understood. CASE SUMMARY: We here report that the erythrocyte sedimentation rate (ESR) increased in a confirmed COVID patient. The high level of ESR sustained for a long time even after the patient recovered from COVID-19, while all results related to tumor, tuberculosis, rheumatic diseases, anemia, etc. cannot explain the abnormal elevation of ESR presented in this case. CONCLUSION: Although the increased ESR cannot be explained by all existing evidence, it possibly links the abnormal pathologic change in some COVID-19 patients and negative prognosis, and provides the clue to dissect the mechanism of illness progressing in COVID-19 and its prognosis.
RESUMEN
In this paper, a deterministic model characterizing the within-host infection of Hepatitis C virus (HCV) in intrahepatic and extrahepatic tissues is presented. In addition, the model also includes the effect of the cytotoxic T lymphocyte (CTL) immunity described by a linear activation rate by infected cells. Firstly, the non-negativity and boundedness of solutions of the model are established. Secondly, the basic reproduction number R01 and immune reproduction number R02 are calculated, respectively. Three equilibria, namely, infection-free, CTL immune response-free and infected equilibrium with CTL immune response are discussed in terms of these two thresholds. Thirdly, the stability of these three equilibria is investigated theoretically as well as numerically. The results show that when R01<1 , the virus will be cleared out eventually and the CTL immune response will also disappear; when R02<1
Asunto(s)
Hepacivirus , Hepatitis C , Humanos , Inmunidad , Modelos Biológicos , Linfocitos T CitotóxicosRESUMEN
Silicon-containing hyperbranched polymers (Si-HBPs) have drawn much attention due to their promising applications. However, the construction of Si-HBPs, especially those containing functional aromatic units in the branched backbones by the simple and efficient Piers-Rubinsztajn (P-R) reaction, has been rarely developed. Herein, a series of novel hyperbranched polycarbosiloxanes were prepared by the P-R reactions of methyl-, or phenyl-triethoxylsilane and three Si-H containing aromatic monomers, including 1,4-bis(dimethylsilyl)benzene, 4,4'-bis(dimethylsilyl)-1,1'-biphenyl and 1,1'-bis(dimethylsilyl)ferrocene, using B(C6F5)3 as the catalyst for 0.5 h at room temperature. Their structures were fully characterized by Fourier transform infrared spectroscopy, 1H NMR, 13C NMR, and 29Si NMR. The molecular weights were determined by gel permeation chromatography. The degrees of branching of these polymers were 0.69-0.89, which were calculated based on the quantitative 29Si NMR spectroscopy. For applications, the ferrocene-linked Si-HBP can be used as precursors to produce functional ceramics with good magnetizability after pyrolysis at elevated temperature.
RESUMEN
In this paper, pure silk protein was extracted from Bombyx mori silks and fabricated into a new kind of disordered bio-microfiber structure using electrospinning technology. Coherent random lasing emission with low threshold was achieved in the silk fibroin fibers. The random lasing emission wavelength can be tuned in the range of 33 nm by controlling the pump location with different scattering strengths. Therefore, the bio-microfiber random lasers can be a wide spectral light source when the system is doped with a gain or energy transfer medium with a large fluorescence emission band. Application of the random lasers of the bio-microfibers as a low-coherence light source in speckle-free imaging had also been studied.
Asunto(s)
Fibroínas/química , Rayos Láser , Luz , Animales , Bombyx , Fibroínas/ultraestructura , Procesamiento de Imagen Asistido por Computador , Dispositivos ÓpticosRESUMEN
The most common self-assembly structure for A2B copolymer is the micellar structure with B/A segments being the core/corona, which greatly limits its application range. Following the principle of structure deciding the properties, a reformation in the molecular structure of A2B copolymer is made by appending three segments of a third component C with the same length to the three arms, resulting (AC)2CB 3-miktoarm star terpolymer. A reverse micellar structure in self-assembly is expected by regulating the C length and the pairwise repulsive strength of C to A/B, aiming to enrich its application range. Keeping both A and B lengths unchanged, when the repulsion strength of C to A is much stronger than C to B, from the results of mesoscopic simulations we found, with a progressive increase in C length, (AC)2CB terpolymer undergoes a transition in self-assembled structures, from a cylindrical structure with B component as the core, then to a deformed lamellar structure, and finally to a cylindrical structure with A component as the core. This reverse micellar structure is formed with the assistance of appended C segments, whose length is longer than half of B length, enhancing the flexibility of three arms, and further facilitating the aggregation of A component into the core. These results prove that the addition of a third component is a rational molecular design, in conjunction with some relevant parameters, enables the manufacturing of the desired self-assembly structure while avoiding excessive changes in the involved factors.
RESUMEN
The Escherichia coli cAMP receptor protein, CRP, is a homodimeric global transcription activator that employs multiple mechanisms to modulate the expression of hundreds of genes. These mechanisms require different interfacial interactions among CRP, RNA, and DNA of varying sequences. The involvement of such a multiplicity of interfaces requires a tight control to ensure the desired phenotype. CRP-dependent promoters can be grouped into three classes. For decades scientists in the field have been puzzled over the differences in mechanisms between class I and II promoters. Using a new crystal structure, IR spectroscopy, and computational analysis, we defined the energy landscapes of WT and 14 mutated CRPs to determine how a homodimeric protein can distinguish nonpalindromic DNA sequences and facilitate communication between residues located in three different activation regions (AR) in CRP that are â¼30 Å apart. We showed that each mutation imparts differential effects on stability among the subunits and domains in CRP. Consequently, the energetic landscapes of subunits and domains are different, and CRP is asymmetric. Hence, the same mutation can exert different effects on ARs in class I or II promoters. The effect of a mutation is transmitted through a network by long-distance communication not necessarily relying on physical contacts between adjacent residues. The mechanism is simply the sum of the consequences of modulating the synchrony of dynamic motions of residues at a distance, leading to differential effects on ARs in different subunits. The computational analysis is applicable to any system and potentially with predictive capability.