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A phase frequency detector (PFD) with a very low dead zone is proposed which is based on a configuration adaptable to both CMOS or carbon nano-tube transistors (CNTFETs). In the first step the proposed configuration is designed using CMOS transistors, and then CNTFETs are substituted to improve the speed and reduce the propagation delay. The proposed PFD in addition to very low dead zone, has low power consumption and high frequency range of operation, which are achieved as a result of the elimination of the reset path. The simulation results based on 32 nm technology for CNTFET and 180 nm technology for CMOS, illustrate that CNTFET-based proposed circuit dissipates 2 µW and has frequency of operation up to 30 GHz, and the dead zone equal to 1 ps. Compared to the conventional PFD based on CMOS technology, its dead zone and power consumption are lower. In addition, the effects of blocks’ parameters including the phase detector, which affect the operation of the phase locked loop, or delay locked loop, are systematically analyzed.

BACKGROUND: The inborn errors of immunity (IEIs) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections besides other complications including autoimmune and inflammatory diseases. In this study, we aim to evaluate clinical, immunological, and molecular data of monogenic IEI patients with and without autoimmune manifestations. METHODS: We have retrospectively screened cases of monogenic IEI in the Iranian PID registry for the occurrence of autoimmunity and immune dysregulation. A questionnaire was filled for all qualified patients with monogenic defects to evaluate demographic, laboratory, clinical, and molecular data. RESULTS: A total of 461 monogenic IEI patients (290 male and 171 female) with a median (IQR) age of 11.0 (6.0-20.0) years were enrolled in this study. Overall, 331 patients (72.1) were born to consanguineous parents. At the time of the study, 330 individuals (75.7) were alive and 106 (24.3) were deceased. Autoimmunity was reported in 92 (20.0) patients with a median (IQR) age at autoimmune diagnosis of 4.0 (2.0-7.0) years. Sixteen patients (3.5) showed autoimmune complications (mostly autoimmune cytopenia) as the first presentation of the disease. Most of the patients with autoimmunity were diagnosed clinically with common variable immunodeficiency (42.4). The frequency of sinusitis and splenomegaly was significantly higher in patients with autoimmunity than patients without autoimmunity. In patients with autoimmunity, the most common pathogenic variants were identified in LRBA (in 21 patients, 23.0), ATM (in 13 patients, 14.0), and BTK (in 9 patients, 10.0) genes. In the evaluation of autoimmunity by different genes, 4 of 4 IL10RB (100), 3 of 3 AIRE (100), 21 of 30 LRBA (70.0) mutated genes had the highest prevalence of autoimmunity. CONCLUSIONS: Autoimmune phenomena are common features among patients with monogenic IEI and are associated with a more complicated course of the disease. Therefore, when encountering autoimmune disorders especially in the setting of dysgammaglobulinemia, it would be appropriate to conduct next generation sequencing (due to phenocopies of IEI genes) to discover responsible genes for the immune dysregulation at an early stage of the disease.

The number of inherited diseases and the spectrum of clinical manifestations of primary immunodeficiency disorders (PIDs) are ever-expanding. Molecular diagnosis using genomic approaches should be performed for all PID patients since it provides a resource to improve the management and to estimate the prognosis of patients with these rare immune disorders. The current update of Iranian PID registry (IPIDR) contains the clinical phenotype of newly registered patients during last 5 years (2013–2018) and the result of molecular diagnosis in patients enrolled for targeted and next-generation sequencing. Considering the newly diagnosed patients (n = 1395), the total number of registered PID patients reached 3056 (1852 male and 1204 female) from 31 medical centers. The predominantly antibody deficiency was the most common subcategory of PID (29.5%). The putative causative genetic defect was identified in 1014 patients (33.1%) and an autosomal recessive pattern was found in 79.3% of these patients. Among the genetically different categories of PID patients, the diagnostic rate was highest in defects in immune dysregulation and lowest in predominantly antibody deficiencies and mutations in the MEFV gene were the most frequent genetic disorder in our cohort. During a 20-year registration of Iranian PID patients, significant changes have been observed by increasing the awareness of the medical community, national PID network establishment, improving therapeutic facilities, and recently by inclusion of the molecular diagnosis. The current collective study of PID phenotypes and genotypes provides a major source for ethnic surveillance, newborn screening, and genetic consultation for prenatal and preimplantation genetic diagnosis.

Background: Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency disorder mainly characterized by recurrent bacterial infections besides other immunological defects including loss of or dysfunction of B cells and decreased immunoglobulin levels. In this study, our aim is to evaluate clinical, immunological, and molecular data of patients with a primary clinical diagnosis of CVID and autoimmune phenotype with a confirmed genetic diagnosis. Methods: Among 297 patients with CVID, who were registered in the Iranian Primary Immunodeficiency Registry at Children’s Medical Center Hospital in Iran, 83 patients have been genetically examined and 27 patients with autoimmunity and confirmed genetic mutations were selected for analysis. Whole-exome sequencing and confirmatory Sanger sequencing methods were used for the study population. A questionnaire was retrospectively filled for all patients to evaluate demographic, laboratory, clinical, and genetic data. Results: In the 27 studied patients, 11 different genetic defects were identified, and the most common mutated gene was LRBA, reported in 17 (63.0%) patients. Two patients (7.7%) showed autoimmune complications as the first presentation of immunodeficiency. Eleven patients (40.7%) developed one type of autoimmunity, and 16 patients (59.3%) progressed to poly-autoimmunity. Most of the patients with mono-autoimmunity (n = 9, 90.0%) primarily developed infectious complications, while in patients with poly-autoimmunity, the most common first presentation was enteropathy (n = 6, 37.6%). In 13 patients (61.9%), the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency. The most frequent autoimmune manifestations were hematologic (40.7%), gastrointestinal (48.1%), rheumatologic (25.9%), and dermatologic (22.2%) disorders. Patients with poly-autoimmunity had lower regulatory T cells than patients with mono-autoimmunity. Conclusion: In our cohort, the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency in most patients. This association highlights the fact that patients referring with autoimmune manifestations should be evaluated for humoral immunity.

[Background] Congenital agammaglobulinemia is the first primary immunodeficiency disorder characterized by a defect in B lymphocyte development and subsequently decreased immunoglobulin levels. These patients are prone to suffer from recurrent infections mostly involving the respiratory tract. In this study, we aimed to describe in detail respiratory tract complications as the most prominent clinical feature among agammaglobulinemic patients., [Methods] A total number of 115 patients were included. Demographic, clinical, and genetic data were collected from the patients’ medical records. Among the available patients, pulmonary function tests (PFTs) and/or high‐resolution computed tomography (HRCT) were performed., [Results] Respiratory tract complications (85.2%) especially pneumonia (62.6%) were the most prominent clinical features in our cohort. Among patients with abnormal PFT results (N = 19), a mixed respiratory pattern was observed in 36.8%. HRCT was carried out in 29 patients; Bhalla scoring‐based evaluation of these patients indicated excellent (44.8%), followed by good (34.5%) and mild (20.7%) results. Bronchiectasis was found in 13 patients undergoing HRCT (44.8%). We found significant inverse correlations between the Bhalla score and incidence rate of pneumonia, as well as the presence of bronchiectasis. Patients with abnormal PFT results had statistically significant higher bronchiectasis frequency and lower Bhalla scores compared to those with normal results. Forty‐one patients were deceased, and here, respiratory failure was the most common cause of death (45.5%)., [Conclusion] High prevalence of respiratory tract infections among agammaglobulinemic patients and subsequent progression to permanent lung damage highlights the importance of implementing respiratory evaluation as part of routine follow‐up program of agammaglobulinemic patients. Physicians should be aware of this and regularly monitor the respiratory function of these patients to allow for timely diagnosis and treatment initiation aiming to improve patients’ prognosis and quality of life., This work was supported by a grant (37023‐154‐04‐96) from Tehran University of Medical Science.

In this paper, a high gain broadband low noise amplifier with flat power gain is designed for using in the wireless systems in frequency range of 2-5.5 GHz. This LNA is designed employing two pHEMT devices which are in cascode while using current reuse structure. The low noise amplifier which is unconditionally stable in the over frequency range of 2-5.5 GHz, is achieved to have maximum power gain of 28.28 dB at 2.25 GHz. Minimum noise figure of the LNA is 0.939 dB. Maximum of input return loss, output return loss and reverse isolation are less than - 10.15 dB, less than - 10.53 dB and below - 39.18, respectively. The LNA consumes DC power of 54.92 mw. The figure of merit (FOM) of proposed broadband LNA was calculated that shows good improvement compared with other works.

In this paper, the channel doping engineering is proposed to improve the benchmarking parameters of the analog/radio frequency and the high frequency noise performance of the junctionless (JL)-In0.3Ga0.7As/GaAs device. The proposed structure is called shell doped of channel-JLFET (SDCh-JLFET). The sub-gate doped layer thickness (D) and middle of channel impurity concentration (Nmiddle) are considered as additional factors to improve the analog/radio frequency parameters and high frequency noise performance of device. The SDCh-JLFET with a channel length of 10 nm, D = 1 nm, and Nmiddle = 2 × 1017cm−3 showed the transconductance of Gmmax = 3mS/um, unity gain cut-off frequency of fT = 700 GHz, the minimum noise figure of Nfmin = 0.84 db and available associated gain of Gass = 28.5 db. The Gmmax, fT, Nfmin and Gass parameters of the SDCh-JLFET device are improved by 76%, 36%, 35% and 26%, respectively, compared to JL-In0.3Ga0.7As/GaAs device without shell doping (JLFET) but with similar dimensions. The SDCh-JLFET device proposed in this paper can be a reasonable candidate for analog/radio frequency applications and high frequency noise.

BACKGROUND: Predominantly antibody deficiencies (PADs) are the most common primary immunodeficiencies, characterized by hypogammaglobulinemia and inability to generate effective antibody responses. OBJECTIVE: We intended to report most common monogenic PADs and to investigate how patients with PAD who were primarily diagnosed as suffering from agammaglobulinemia, hyper-IgM (HIgM) syndrome, and common variable immunodeficiency (CVID) have different clinical and immunological findings. METHODS: Stepwise next-generation sequencing and Sanger sequencing were performed for confirmation of the mutations in the patients clinically diagnosed as suffering from agammaglobulinemia, HIgM syndrome, and CVID. RESULTS: Among 550 registered patients, the predominant genetic defects associated with agammaglobulinemia (48 Bruton's tyrosine kinase BTK and 6 mu heavy chain deficiencies), HIgM syndrome (21 CD40 ligand and 7 activation-induced cytidine deaminase deficiencies), and CVID (17 lipopolysaccharides-responsive beige-like anchor deficiency and 12 atypical Immunodeficiency, Centromeric instability, and Facial dysmorphism syndromes) were identified. Clinical disease severity was significantly higher in patients with mu heavy chain and CD40 ligand mutations compared with patients with BTK (P = .003) and activation-induced cytidine deaminase (P = .009) mutations. Paralysis following live polio vaccination was considerably higher in patients with mu heavy chain deficiency compared with BTK deficiency (P < .001). We found a genotype-phenotype correlation among patients with BTK mutations regarding clinical manifestation of meningitis and chronic diarrhea. Surprisingly, we noticed that first presentations in most patients with Immunodeficiency, Centromeric instability, and Facial dysmorphism were respiratory complications (P = .008), whereas first presentations in patients with lipopolysaccharides-responsive beige-like anchor deficiency were nonrespiratory complications (P = .008). CONCLUSIONS: This study highlights similarities and differences in the clinical and genetic spectrum of the most common PAD-associated gene defects. This comprehensive comparison will facilitate clinical decision making, and improve prognosis and targeted treatment.

This paper presents a novel design for a ternary successor and predecessor using carbon nanotube field-effect transistors (CNTFETs). The chirality of the CNTFETs is utilized for threshold voltage control. The proposed designs are simulated and examined, using Synopsys HSPICE with Standard 32 nm CNTFET technology in various situations. Simulation results demonstrate the correct and high-performance operation of the proposed circuits even in the presence of process variations. It is shown that the proposed ternary circuits achieve a significant saving in energy consumption (95.18 % for successor and 91 % for predecessor) compared with previously presented designs.

With the development of analog integrated circuits technology and due to the complexity, and various types of faults that occur in analog integrated circuits, fault detection is a new idea, has been studied in recent decades. In this paper a three amplifier state variable filter is used as circuit under test (CUT) and, a hybrid neural network is proposed for soft fault diagnosis of the CUT. Genetic algorithm (GA) has the powerful ability of searching the global optimal solution, and back propagation (BP) algorithm has the feature of rapid convergence on the local optima. The hybrid of two algorithm will improve the evolving speed of neural network. GA-BP scheme adopts GA to search the optimal combination of weights in the solution space, and then uses BP algorithm to obtain the accurate optimal solution quickly. Experiment results show that the proposed GA-BP scheme is more efficient and effective than BP algorithm.

Since in designing the full adder circuits, full adders have been generally taken into account, so as in this paper it has been attempted to represent a full adder cell with a significant efficiency of power, speed and leakage current levels. For this objective, a comparison between five full adder circuits has been provided. Applying floating gate technology and refresh circuits in the full adder cell lead to the reduction of leakage current on the gate node. The simulations were accomplished in this paper, through HSPICE software and 65 nm CMOS technology. The simulation results indicate the considerable efficiency of power consumption, speed and leakage current in the full adder cell rather than other cells.

This paper presents a new method for pixel-level image fusion of multi-focus images based on the fuzzy approach with a particular view of human's experiences. This method is different from traditional image fusion methods and eventuate the best results by using intelligent algorithms. The proposed fuzzy system has two inputs that are the two corresponding pixels in each image. Fuzzy rules determine the output values of each pixel. The system is simulated with MATLAB Simulink and the results of the simulation are compared with common algorithms such as pixel averaging.

A novel DC gain enhancement technique for cascoded structure amplifiers is proposed. It employs a positive feedback to increase the DC gain without affecting the bandwidth and power consumption of the amplifier. Compared to the conventional gain boosting technique, the presented approach achieves the same gain with much less power consumption. Circuit level simulation and analysis results are provided to show the effectiveness of the proposed technique.

In this paper, designing an ultra wideband 3–5 GHz CG LNA in two different styles with active and passive output matching using 0.18 µm CMOS process is presented. A wider bandwidth and reduced linearity is observed in active output whereas in passive mode a better performance of linearity but reduced bandwidth is achieved. As the circuitry in active mode to increase linearity and having a more excess transistor, dissipation is more in comparison with passive one. Using a shunt-series broadening technique at the output of the main stage has a roll of optimization of gain and controlling the bandwidth. By using a 1.8 v power supply a power gain of more than 10.5 dB, input reverse isolation less than −10.3 dB noise figure of about 4 dB and IIP3 in center frequency of 4 GHz about −4.4 dBm which dissipates less than 12 mw in active mode in 3–5.5 GHz frequency band is observed. In passive output mode with reduced dissipation, using 1.2 v power supply a power gain of more than 10 dB, input reverse isolation less than −10 dB, noise figure of about 4 dB and IIP3 in center frequency of 4 GHz about −2.5 dBm with dissipation of less than 6mw in 3–5 GHz frequency band is attained.

Semiconductor of ZnO has been extensively researched in recent years for its extraordinary properties. ZnO is naturally an n-type semiconductor and due to asymmetric doping limitations, it is difficult to obtain p-type ZnO. In this work the deposited nitrogen doped zinc oxide nano films by reactive magnetron sputtering technique, were treated using conventional thermal annealing, while, the annealing temperature were varied from 300 °C to 800 °C in a mixture of nitrogen and oxygen ambient. The surface morphology, Crystallinity and electrical characteristics of prepared films have been investigated with respect to the temperature of annealing process. The XRD spectra of samples before and after annealing processes confirmed the deposition of wurtzite crystalline structures of ZnO. However, the annealed samples exhibited smaller FWHM compared to un-annealed ones, which confirms better crystalline structure of annealed films. Moreover, un-annealed specimens showed n-type conductivity with an electron concentration of 2.5×1016 cm−3, while the annealed samples exhibited p-type behavior with a hole concentration of 8.2×1015 cm−3.

Recently, by increasing the usage of battery-powered systems such as laptop, mobile, wristwatch and etc. power dissipation is becoming an important constraint in each electronically design. To reduce the power dissipation, it has been offered to use a floating gate MOSFET technology. According to decline the size of the circuits and power dissipation, thickness of the gate oxide will decrease and this causes a big leakage current in the VLSI circuits. So, new methods should be recommended to maintain the charges in the nodes. In this paper we try to present a new Quasi FGMOS technique to solve this problem. Simulations in a 65 nm process show that by using our proposed Quasi FGMOS, there will be lower PDP and also leakage current than conventional Quasi FGMOSs have.

The fundamental role of pulmonary vascular resistance in the Fontan circulation is obvious. Medications decreasing this resistance may have an impact on the fate of this population. Hence, we assessed noninvasively the effect of oral sildenafil on the ventriculo-arterial coupling in patients with Fontan circulation. In a single-center, prospective case series study, 23 patients with fenestrated extracardiac total cavopulmonary connection age 12-31 years were enrolled in this study. Clinical characteristics and echocardiographic examination were performed before and after a 1 week course of sildenafil at 0.5 mg/kg every 8 h. Sildenafil had no effect on heart rate and blood pressure. However, oxygen saturation was significantly increased with sildenafil (87.6 ± 4.3 vs. 90.1 ± 3.6; P < 0.0001). The calculated noninvasive ventricular end-systolic elastance (Ees) was greater after sildenafil compared with the pre-sildenafil values (1.59 ± 0.17 vs. 1.72 ± 0.27 mm Hg/ml; P = 0.001). Moreover, significant decreases in arterial elastance (Ea) (1.62 ± 0.53 vs. 1.36 ± 0.43 mm Hg/ml; P < 0.0001), ventricular end-diastolic elastance (Eed) (0.05 ± 0.021 vs. 0.04 ± 0.013; P = 0.002), and, finally, ventriculo-arterial coupling index (0.99 ± 0.26 vs. 0.76 ± 0.15; P < 0.0001) were found after sildenafil administration. The intolerable side effects that led to stopping the sildenafil occurred only in one (4 %) patient. Sildenafil has increased ventricular systolic elastance and improved ventriculo-arterial coupling in patients palliated with Fontan circulation. Short-term sildenafil was well tolerated in most of the patients with only minor side effects.

In this paper, a low-noise CMOS amplifier operating at a 2.5 supply voltage is presented and developed by using the noise reduction technique chopper stabilization. Chopper stabilization is a technique used to reduce the effects of flicker noise and offset. The low-noise amplifier fabricated by a 0.18-µm CMOS technology was measured at 2.5 V performance of 5-nV/Sqrt(Hz) input noise at 1-KHz chopping frequency 1-nV/Sqrt(Hz) input noise at 3-KHz chopping frequency that is considerable compared to previous results.

In this paper, a new correction method in analog design automation system is presented. This new method uses the concepts of fuzzy logic to correct the failed designs. Improvement of failed circuit performance affects the design parameters and other performances. We use fuzzy linguistic terms to express the qualitative dependence between design parameters and circuit performances. Circuit correction process deals with different correction ways. We use fuzzy system to model these correction branches and select the best one with minimum cost.

This study was a randomized, open label comparison that was designed to determine efficacy and safety of miltefosine as the first oral drug for the treatment of zoonotic cutaneous leishmaniasis caused by Leishmania major in comparison with meglumine antimoniate. Complete clinical response was defined as 100% re-epithelialization of the lesion. Definitions of lesion cure and failure were based on both clinical and parasitological criteria two weeks after the end of treatment and clinical recovery three months after this period. Of 32 patients enrolled for miltefosine treatment 28 patients completed treatment, of which 26 were cured at three months, corresponding to a cure rate of 92.9% on a per protocol analysis, and 81.3% according to intention to treat analysis. There was one failure (3.1%), one relapse (3.1%) and four dropouts due to lack of tolerability (12.5%) during the first week of treatment. Of 31 patients who received intramuscular meglumine antimoniate (20mgSb(5)/kg body weight daily for 14 days) 25 were cured (83.3% on a per protocol basis, 80.6% on intention to treat basis), five failed (16.1%) and one was lost (3.2%) at 3-month follow-up. At 6-month follow-up after the end of treatment, no relapse was observed. Both regimens were tolerated but averages of nausea (32.2%) and vomiting (21.5%) were observed in patients during two weeks after initiation of miltefosine treatment. Other gastrointestinal, musculoskeletal, and total adverse events were not statistically different in the two groups during one to four weeks after therapy initiation. No relevant changes were observed in levels of liver enzymes, creatinine and hematological tests before and after end of treatment in both groups. In conclusion, miltefosine is apparently at least as good as meglumine antimoniate for the treatment of cutaneous leishmaniasis caused by L. major in Iran, based on parasitological as well as clinical criteria two weeks, three months, and six months after end of treatment.

In this paper an intelligent CAD tool for the design of analog circuits is presented. First, the system uses fuzzy rule based reasoning to select alternative architectures for the circuits at each level of hierarchy and then deduces the device sizes via case-based reasoning whose objective is to determine the plausible building blocks subspecifications on the basis of past design experiences. In the case that there are some specifications which have not been met yet, qualitative reasoning-based approach would be used to make final correction. The above approach is demonstrated through the example of a CMOS op-amp.