Chemical protein synthesis-assisted high-throughput screening strategies (e.g., mirror-image phage display, mirror-image one-bead one-compound approaches) for d-peptide ligands were reviewed.
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d-peptides are recognized as a new class of synthetic chemical drugs and they possess many interesting advantages such as high enzymatic stability, improved oral bioavailability, as well as high binding affinity and specificity. Recently, d-peptide drugs have been attracting increasing attention in both academic and industrial researches over recent years. One d-peptide etelcalcetide has even entered the market that targets the calcium (Ca2+)-sensing receptor (CaSR) to fight secondary hyperparathyroidism. Effective discovery and optimization of d-peptide ligands that can bind to various disease-related targets with high specificity and potency is of great importance for the development of d-peptide drugs. This review surveys the recent method development in this area especially the chemical protein synthesis-assisted high-throughput screening strategies for d-peptide ligands and their application in drug discovery.
Learning a script with mirrored graphs (e.g., d ≠ b) requires overcoming the evolutionary-old perceptual tendency to process mirror images as equivalent. Thus, breaking mirror invariance offers an ...important tool for understanding cultural re-shaping of evolutionarily ancient cognitive mechanisms. Here we investigated the role of script (i.e., presence vs. absence of mirrored graphs: Latin alphabet vs. Tamil) by revisiting mirror-image processing by illiterate, Tamil monoliterate, and Tamil-Latin-alphabet bi-literate adults. Participants performed two same-different tasks (one orientation-based, another shape-based) on Latin-alphabet letters. Tamil monoliterate were significantly better than illiterate and showed good explicit mirror-image discrimination. However, only bi-literate adults fully broke mirror invariance: slower shape-based judgments for mirrored than identical pairs and reduced disadvantage in orientation-based over shape-based judgments of mirrored pairs. These findings suggest learning a script with mirrored graphs is the strongest force for breaking mirror invariance.
Abstract Background Whether second-generation antipsychotic long-acting injection (SGA-LAI) reduces psychotic symptoms at relapse compared with oral antipsychotics remains unclear. The present study ...investigated the effects of SGA-LAI on the time (in hours) of restrictive interventions in hospitalization by conducting a retrospective observational 4-year mirror-image study at a single medical center in Japan. Method We performed a retrospective observational mirror-image study conducted between November 2013 and January 2018. Data were initially retrieved from 101 patients. The 38 patients with schizophrenia who met the inclusion criteria were enrolled in the analysis. The primary outcome was the time of restrictive interventions and the secondary outcomes included the number of hospitalizations (total, voluntary, and involuntary) and bed days compared 2 years before and after initiating SGA-LAI. The restrictive interventions were defined as seclusion and physical restraints. Results The mean time of restrictive interventions significantly decreased from 43.7 to 3.03 ( P = 0.021). The number of admissions and the total number of bed days in post–SGA-LAI fell from 1.03 to 0.61 ( P = 0.011) and 130 to 39.3 ( P = 0.003), respectively, compared with pre–SGA-LAI. In particular, the number of involuntary admissions was significantly reduced (0.50–0.26, P = 0.039). Conclusions The findings indicate that SGA-LAI reduced the time of restrictive interventions and the number of involuntary admissions. Moreover, SGA-LAI may contribute to mild psychiatric symptoms during relapse.
Mirror-image is a term to describe a physical characteristic of some identical twins that appear asymmetrically on opposite sides as if they are looking in a mirror. Mirror-image anisometropia in ...monozygotic twins was previously reported in the ophthalmic literature. In this article, we describe a case of mirror-image hypermetropic anisometropia in siblings aged 8 and 5 years old. Nontwin brothers, 8 and 5 years old, with mirror-image hypermetropic anisometropia, were referred to the pediatric ophthalmology clinic. Corrected distant visual acuity was 20/20 (ocula dextra OD), 20/60 (ocula sinistra OS) in the older brother, and 20/50 (OD), 20/20 (OS) in the younger brother. Cycloplegic refraction was + 3.5 - 1.25 × 180 (OD), +7.75 - 1.5 × 30 (OS), and + 7.0 - 0.75 × 20 (OD), +2.0 - 1.0 × 170 (OS) in the older and younger brother, respectively. The axial length difference between the two eyes was 1.47 mm in the older and 2.01 mm in the younger brother. Hypermetropic anisometropia that may lead to anisometropic amblyopia may happen in nontwin brothers. This emphasizes the importance of complete ophthalmologic examination in the siblings of all patients with anisometropia.
The low response rate and adaptive resistance of PD‐1/PD‐L1 blockade demands the studies on novel therapeutic targets for cancer immunotherapy. We discovered that a novel immune checkpoint TIGIT ...expressed higher than PD‐1 in many tumors especially anti‐PD‐1 resistant tumors. Here, mirror‐image phage display bio‐panning was performed using the d‐enantiomer of TIGIT synthesized by hydrazide‐based native chemical ligation. d‐peptide DTBP‐3 was identified, which could occupy the binding interface and effectively block the interaction of TIGIT with its ligand PVR. DTBP‐3 showed proteolytic resistance, tumor tissue penetrating ability, and significant tumor suppressing effects in a CD8+ T cell dependent manner. More importantly, DTBP‐3 could inhibit tumor growth and metastasis in anti‐PD‐1 resistant tumor model. This is the first d‐peptide targeting TIGIT, which could serve as a potential candidate for cancer immunotherapy.
The d‐peptide DTBP‐3 was identified, which could effectively block TIGIT/PVR interaction. DTBP‐3 could inhibit tumor growth and metastasis in anti‐PD‐1 resistant tumor model and could serve as a potential candidate for cancer immunotherapy.
Mirror image sensory dysfunction (MISD) after breast surgery has not yet been studied. This prospective observational study aimed to determine the incidence of MISD, persistent postoperative pain ...(PPP) and mirror image pain (MIP) during 6 months after total unilateral mastectomy.Visual analogue scale (VAS), Neuropathic Pain Symptom Inventory (NPSI), Pain Catastrophizing Scale (PCS), Hospital Anxiety and Depression Scale (HADS), Life orientation test (LOT) and Quantitative Sensory Testing (QST) (in ipsi and contralateral breast, axilla and thigh) were recorded. VAS > 3 at 1, 3, and 6 postoperative months was considered PPP. Contralateral changes of QST at any time was considered indicative of MISD and spontaneous contralateral VAS ≥ 1 as MIP.Sixty-four patients were included. PPP at 1, 3 and 6 months was 18.8%, 56.2%, and 21.3%, respectively Ten patients presented MIP. MISD was detected in 79.7% patients in contralateral breast and 62.5% in contralateral axilla. Furthermore, changes in QST were present in 39.1% of patients in thigh. Electronic Von Frey (EVF) changes in both contralateral breast and axilla, and in thigh significantly diminished at all postoperative times. Changes of postoperative EVF ≥ 20% in contralateral breast were associated to higher VAS values. NPSI scores were significantly higher at all postoperative times. At 1 month, PCS, depression HADS subscale and LOT scores were significantly worse than all the other periods.MISD incidence was almost 80%, and 15.6% of patients showed spontaneous contralateral VAS ≥ 1. At 6 months 21.3% of patients manifested PPP. The worst alteration of factors related to PPP occurred at 1 postoperative month. Most consistent QST was EVF.
•The solutions of three contact forms (spherical, conical, and cylindrical contact) expressed by elementary functions in two structural forms (“film with two free boundaries” and “film/rigid ...substrate”) are presented.•The influence law of “substrate effect” on indentation curve is analyzed.•Poisson’s ratio has little influence on Pz-a curve, which is affected by elastic modulus a lot.•The measurement method of thin film material parameters is given with considering substrate effect.
The development of contact theories for films is valuable for high-precision machining and measurement. Accordingly, accurate contact mechanics theories for films under common indenter loading are established based on the constitutive equations and potential theory method, Here, the film structures are “film with two free boundaries” and “film/rigid substrate.” The displacement and stress at arbitrary positions can be obtained using exact solutions represented by elementary functions. The application of the foregoing theories to resolve the contact problem encountered in films is convenient for engineers. The influences of substrate and film parameters on contact radius and indentation depth were analyzed. Indentation curves are slightly influenced by Poisson’s ratio, but primarily affected by the elastic modulus. An effective method for measuring of film material parameters is presented. Using numerical software platforms, the method’s analytic algorithm can be transformed into numerical codes and be integrated into special software.
Three‐dimensional virtual dissection using high‐definition live tissue rendering ultrasound tool of a 23‐week gestation fetus with situs solitus, mirror image dextrocardia, ventricular septal defect, ...aortic override, and pulmonary atresia.
A central goal in research on visual perception is to understand how the visual system represents the shapes of objects. According to many theorists, axes defined on the basis of object geometry ...provide a coordinate system for representing the locations and orientations of object parts. An important question that has received little attention concerns how object axes are defined-that is, what aspects of object geometry determine how axes are assigned to shapes? We evaluated 2 hypotheses. According to the elongated-part hypothesis, axes are defined on the basis an object's most elongated part, such that, for example, the principal axis for a hatchet would coincide with the long axis of the hatchet's handle. In contrast, the global-shape hypothesis holds that axes are defined on the basis of an object's overall shape (e.g., for the hatchet, as the longest axis that spans the entire hatchet). Using a novel paradigm involving analysis of mirror-image confusions, we obtained evidence strongly supporting the elongated-part hypothesis. Our results also point to a role for secondary as well as principal axes in object shape representation.
Public Significance Statement
A major function of the brain's visual system is to determine the shapes of objects so that we can recognize and interact with them. In cognitive science, a prominent theoretical view holds that the visual system analyzes objects into parts and determines how the parts are arranged with respect to axes projected onto the object. This study probed how the visual system defines these object axes. Using a novel method in which participants viewed objects and then attempted to recall how they were oriented, we found evidence that the visual system defines object axes on the basis of an object's most elongated part (e.g., the handle of a hatchet) and not by reference to the object's overall shape (e.g., considering the blade as well as the handle of the hatchet). These results advance our understanding of visual object perception and could also have implications for computer vision research and for understanding object perception deficits resulting from brain damage.
Surgical management of the scimitar syndrome Chowdhury, Ujjwal K.; Anderson, Robert H.; Sankhyan, Lakshmi K. ...
Journal of cardiac surgery,
October 2021, 2021-10-00, 20211001, Letnik:
36, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Background and Aim
We sought to address the varied anatomical details, the diagnostic challenges, associated cardiopulmonary anomalies, the techniques, and outcomes of management, including ...re‐interventions of scimitar syndrome.
Methods
A total of 92 published investigations of scimitar syndrome were reviewed. Diagnostic information was provided by clinical presentations, radiographic findings, transthoracic and transesophageal echocardiography, computed‐tomographic angiography, magnetic resonance imaging, angiocardiography, and ventilation/perfusion scans. These investigations served to elucidate the origin, course, and termination of the scimitar vein, the intracardiac anatomy, the presence of associated defects, and the patterns of any accompanying pulmonary lesions prior to surgical intervention.
Results
Of the patients described, up to four‐fifths presented during infancy, with cardiac failure, increased pulmonary flow, and pulmonary hypertension. Associated cardiac and extracardiac defects, particularly hypoplasia of the right lung, are present in up to three‐quarters of cases. Overall operative mortality has been cited between 4.8% and 5.9%. Mortality was highest in patients with preoperative pulmonary hypertension, and those undergoing surgery in infancy. Despite timely surgical intervention, post‐repair obstruction of the scimitar vein, intra‐atrial baffle obstruction, or stenosis of the inferior caval vein were reported in up to two‐thirds of cases. The venous obstruction could not be related to any particular surgical technique. On long term follow‐up, one sixth of patients reported persistent dyspnoea and recurrent respiratory infections.
Conclusions
Any infants presenting with heart failure, right‐sided heart, and hypoplastic right lung should be evaluated to exclude the syndrome. An increased appreciation of variables will contribute to improved surgical management.
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