Miracle-dz/UniFAR-FTUs huggingface dataset:
Age‐related and regional differences in dopamine transporter mRNA expression in human midbrain

We assessed the abundance of dopamine transporter messenger RNA (DAT mRNA) in various human midbrain dopamine cell groups using in situ hybridization. The youngest individuals studied (17–23 years of age) exhibited significant regional heterogeneity of DAT expression, both in terms of the number of dopamine neurons expressing DAT mRNA and the abundance of DAT mRNA per cell, with the highest levels of expression evident within the ventral tier of the substantia nigra and lowest expression within the retrorubral field. In the older subjects (65–72 years old) analyzed, DAT mRNA in all regions was reduced to the level seen in the retrorubal field, indicating a positive correlation between initial levels of DAT expression and subsequent age-related reductions, with some regions exhibiting up to a 75% loss of DAT mRNA with age. The age-related decline in DAT mRNA was due to both a decrease in the abundance of DAT mRNA per dopamine cell as well as a decrease in the total number of dopamine cells expressing DAT mRNA, although tyrosine hydroxylase expression was less affected. These results indicate that changes in dopamine neurotransmission seen in normal aging may be related to altered DAT gene expression.
TRIPLING FORMULAE OF ELLIPTIC CURVE OVER BINARY FIELD IN LOPEZ-DAHAB MODEL

In elliptic curve cryptosystem (ECC), scalar multiplication is the major and most costly operation. Scalar multiplication involves with point operations such as point addition, point doubling, and point tripling. Scalar multiplication can be improved by using efficient point operations. This research focuses on point tripling operation for elliptic curves over the binary field in Lopez-Dahab (LD) model. Currently, there is no existing tripling formula for this model. Traditionally, tripling is computed using one doubling followed by one addition (i.e. 3P=2P+P) with cost of 18M+8S, where M is field multiplication and S is field squaring. In this paper, we proposed tripling formulae with cost of 12M+7S. We proved the formulae and proposed its algorithm. The tripling saved 6M+1S which contribute to cost reduction in multiplication and squaring by 33% and 12.5% respectively when compared with the traditional method. For National Institute of Standards and Technology (NIST) curve (i.e. where a = 1), the cost of the tripling is further reduced to 10M+7S which saved 8M+1S from the traditional one. Further cost reduction in multiplication and squaring by 44% and 12.5% respectively.
Ecological Constraints Limit the Fitness of Fungal Hybrids in the Heterobasidion annosum Species Complex

ABSTRACT The ability of two closely related species to maintain species boundaries in spite of retained interfertility between them is a documented driving force of speciation. Experimental evidence to support possible interspecific postzygotic isolation mechanisms for organisms belonging to the kingdom Fungi is still missing. Here we report on the outcome of a series of controlled comparative inoculation experiments of parental wild genotypes and F1 hybrid genotypes between closely related and interfertile taxa within the Heterobasidion annosum fungal species complex. Results indicated that these fungal hybrids are not genetically unfit but can fare as well as parental genotypes when inoculated on substrates favorable to both parents. However, when placed in substrates favoring one of the parents, hybrids are less competitive than the parental genotypes specialized on that substrate. Furthermore, in some but not all fungus × plant combinations, a clear asymmetry in fitness was observed between hybrids carrying identical nuclear genomes but different cytoplasms. This work provides some of the first experimental evidence of ecologically driven postzygotic reinforcement of isolation between closely related fungal species characterized by marked host specificity. Host specialization is one of the most striking traits of a large number of symbiotic and parasitic fungi; thus, we suggest the ecological mechanism proven here to reinforce isolation among Heterobasidion spp. may be generally valid for host-specialized fungi. The validity of this generalization is supported by the low number of known fungal hybrids and by their distinctive feature of being found in substrates different from those colonized by parental species.
Induction of CD4 expression and human immunodeficiency virus type 1 replication by mutants of the interferon-inducible protein kinase PKR

Replication of the human immunodeficiency virus type 1 (HIV-1) is inhibited by interferons (IFNs), and the IFN-inducible protein kinase PKR is thought to mediate this effect by regulating protein synthesis. Here we report that ectopic expression of dominant negative PKR mutants in Jurkat cells induces HIV-1 replication. Specifically, expression of CD4 is upregulated by the PKR mutants, and this correlates with an induction of HIV-1 binding and proviral DNA synthesis upon HIV-1 infection. Moreover, activation of NF-kappaB was induced by an RNA binding-defective mutant of PKR. Thus, it appears that PKR, in addition to translational control, is involved in HIV-1 replication by modulating virus binding through the regulation of CD4 expression and virus gene expression through the activation of NF-kappaB.
Protection against Tetanus by Needle-Free Inoculation of Adenovirus-Vectored Nasal and Epicutaneous Vaccines

ABSTRACT The effectiveness of vaccination programs would be enhanced greatly through the availability of vaccines that can be administered simply and, preferably, painlessly without the need for timed booster injections. Tetanus is a prime example of a disease that is readily preventable by vaccination but remains a major threat to public health due to the problems associated with administration of the present vaccine. Here we show that a protective immune response against liveClostridium tetani infection in mice can be elicited by an adenovirus vector encoding the tetanus toxin C fragment when administered as a nasal or epicutaneous vaccine. The results suggest that these vaccination modalities would be effective needle-free alternatives. This is the first demonstration that absorption of a small number of vectored vaccines into the skin following topical application of a patch can provide protection against live bacteria in a disease setting.
Clevidipine in Adult Cardiac Surgical Patients: A Dose-finding Study

Background Treatment of elevated blood pressure is frequently necessary after cardiac surgery to minimize postoperative bleeding and to attenuate afterload changes associated with hypertension. The purpose of this study was to investigate the pharmacodynamics and pharmacokinetics of a short-acting calcium channel antagonist, clevidipine, in the treatment of hypertension in postoperative cardiac surgical patients. Methods Postoperative cardiac surgical patients were randomized to receive placebo or one of six doses of clevidipine. Hemodynamic parameters were recorded and blood samples were drawn for determination of clevidipine plasma concentrations during infusion and after discontinuation of clevidipine. The concentration–response relation was analyzed using logistic regression, and pharmacokinetic models were applied to the data using population analysis. Results There were significant decreases in mean arterial blood pressure and systemic vascular resistance at doses greater than or equal to 1.37 &mgr;g · kg−1 · min−1. There were no changes in heart rate, central venous pressure, pulmonary artery occlusion pressure, or cardiac index with increasing doses of clevidipine. The clevidipine C50 value for a 10% or greater decrease in mean arterial pressure was 9.7 &mgr;g/l and for a 20% or greater decrease in mean arterial pressure was 26.3 &mgr;g/l. The pharmacokinetics of clevidipine were best described with a three-compartment model with a volume of distribution of 32.4 l and clearance of 4.3 l/min. The early phase of drug disposition had a half-life of 0.6 min. The context-sensitive half-time is less than 2 min for up to 12 h of administration. Conclusion Clevidipine is a calcium channel antagonist with a very short duration of action that effectively decreases systemic vascular resistance and mean arterial pressure without changing heart rate, cardiac index, or cardiac filling pressures.
Loss of RAD-23 Protects Against Models of Motor Neuron Disease by Enhancing Mutant Protein Clearance

Misfolded proteins accumulate and aggregate in neurodegenerative disease. The existence of these deposits reflects a derangement in the protein homeostasis machinery. Using a candidate gene screen, we report that loss of RAD-23 protects against the toxicity of proteins known to aggregate in amyotrophic lateral sclerosis. Loss of RAD-23 suppresses the locomotor deficit of Caenorhabditis elegans engineered to express mutTDP-43 or mutSOD1 and also protects against aging and proteotoxic insults. Knockdown of RAD-23 is further neuroprotective against the toxicity of SOD1 and TDP-43 expression in mammalian neurons. Biochemical investigation indicates that RAD-23 modifies mutTDP-43 and mutSOD1 abundance, solubility, and turnover in association with altering the ubiquitination status of these substrates. In human amyotrophic lateral sclerosis spinal cord, we find that RAD-23 abundance is increased and RAD-23 is mislocalized within motor neurons. We propose a novel pathophysiological function for RAD-23 in the stabilization of mutated proteins that cause neurodegeneration. SIGNIFICANCE STATEMENT In this work, we identify RAD-23, a component of the protein homeostasis network and nucleotide excision repair pathway, as a modifier of the toxicity of two disease-causing, misfolding-prone proteins, SOD1 and TDP-43. Reducing the abundance of RAD-23 accelerates the degradation of mutant SOD1 and TDP-43 and reduces the cellular content of the toxic species. The existence of endogenous proteins that act as “anti-chaperones” uncovers new and general targets for therapeutic intervention.
Epidural Injections of Indomethacin for Postlaminectomy Syndrome: A Preliminary Report

Since there have been side effects reported with the administration of corticosteroids epidurally, their application has been limited. Because some nonsteroidal antiinflammatory drugs have central and spinal antinociceptive actions, we have compared the effects of indomethacin (INM) given by the epidural route to methylprednisolone (MTP). This was a prospective, comparative study in an ambulatory pain care center. Two hundred six patients with recurrent low back pain (Visual Analog Scale >7) and radiculopathy after they had had 2 or more lumbar laminectomies with the diagnosis of “postlaminectomy syndrome” were randomly assigned to 1 of 3 groups. Group I (64 patients) was given 2 epidural injections of lyophilized INM 1 mg. Group II (60 patients) received 2 injections of 2 mg of INM at the same intervals. Group III (82 patients) was treated by 2 epidural injections of MTP 80 mg. In every case, the medication was diluted in 3 mL of 0.5% bupivacaine. Reductions of pain were assessed by changes in the Visual Analog Scale; physical activities, attitude, and medication intake were graded by the Pain Progress Score recorded before each treatment and 2 wk after the last. After each injection, all patients had pain relief to Visual Analog Scale <3. Increased analgesia (P < 0.05) was noted when a double dose of INM was used (Group II) or when 80 mg of MTP was given. The total average scores of the Pain Progress Score showed significant differences at the second injection in Groups II and III only. Physical activity, emotional attitudes, and medication intake were also improved but the changes were not statistically significant. In conclusion, in this group of patients, INM produced adequate analgesia in Groups I and II, with evidence suggesting that 2 mg of INM may produce a similar degree of pain relief as 80 mg of MTP after the second injection. Other nonsteroidal antiinflammatory drugs may be explored in the future for the same purpose.
A photonic approach to broadband microwave frequency measurement

A novel photonic approach to microwave frequency measurement based on interference effect of microwave signals is proposed. In the simple measurement system, an unknown microwave signal is modulated simultaneously on two optical carriers with different wavelengths through a Mach-Zehnder modulator (MZM). The optical output from the MZM propagates in a dispersive medium, leading to different phase shifts. By scanning the wavelength of one optical carrier, the frequency of the microwave signal can be obtained directly through analyzing the interference intensity of the microwave signal from the photodetector. The validity of the proposed approach is demonstrated experimentally by obtaining the unknown microwave frequency from 1 to 15GHz.
[Comparison of transient evoked otoacoustic emissions in newborns and adults with frequency specific approach].

OBJECTIVE To investigate the difference of transient evoked otoacoustic emissions (TEOAE) between neonates and adults with the frequency-specific approach. METHODS TEOAE were recorded from 112 newborns (62 females, 58 males) who passed hearing screening, and 32 adults (17 females, 15 males) tested with pure-tone threshold equal or less than 20 dBHL. Band reproducibility, signal-to-noise rate (SNR) of frequency-band and half-octave frequency analysis of TEOAE amplitude was recorded respectively. RESULTS Significant differences were found in two groups, the higher entire TEOAE level found in newborn [(15.18 +/- 4.39) dB SPL] was higher than that of adults group [(9.51 +/- 4.12) dB SPL, P < 0.05]. The lowest wave reproducibility and SNR were in first frequency band (0.8 kHz) for neonate, and then, in last frequency band (4.0 kHz) were for young adults. For newborns, the highest band reproducibility and SNR were presented at fourth frequency band (3.2 kHz). However, for adults, the highest band reproducibility and SNR were presented at second frequency band (1.5 kHz). Frequency space of the SNR response peaks between neonates and adults was 1.7 kHz. The level difference was 7.09 dB SPL. Half octave frequency analysis shows a TEOAE response peaks in neonates was (10.50 +/- 5.09) dB SPL at the 2828 Hz, and in adults, it was (2.84 +/- 5.33) dB SPL at the 1414 Hz. Frequency space of the TEOAE response peaks between neonates and adults was 1414 Hz. Level differences of TEOAE response peaks was 7.66 dB SPL. TEOAE response peak in adult appear at 1.5 kHz, and then dropped down correlated to increase of frequency. From the first to the last testing frequency band, the difference of TEOAE level between neonate and adult was found to increase correlated to increase of frequency. CONCLUSIONS TEOAE response level in newborn is higher than that in adult group. Further, the decrease of TEOAE response level presented more sharpens with the frequency increasing in adult. The frequency of TEOAE response peak in neonate (3.2 kHz) is higher than adult (1.5 kHz). The level of TEOAE response peak is also greater than adult.
Iterative physical optics (IPO) with integral evaluation of self-shadowing

A novel iterative physical optics (IPO) algorithm is proposed, for the analysis of scattering from large complex geometries involving multiple reflections and complex self-shadowing effects. The algorithm involves two types of nested iterations: reflection (“bounce”) iterations and self-shadowing iterations. At each bounce iteration, the physical optics sources induced on the surface of the scatterer produce a correction to the incident field, which in turn creates a correction to the physical optics sources. Each correction is evaluated to account for self-shadowing effects by a nested iterative evaluation of shadow-radiation integrals. The nested iterative formulation is naturally accelerable by using fast field evaluation methods, e.g., the multilevel non-uniform grid algorithm. The procedure's applicability to complex geometries is demonstrated numerically by comparison to numerically exact results and to standard PO results.
Interleukin‐12 primes CD4+ T cells for interferon‐γ production and protective immunity during Mycobacterium avium infection

Interleukin‐12 (IL‐12) is a crucial cytokine for the generation of a protective immune response against Mycobacterium avium infection. In contrast to infected control mice, IL‐12‐deficient mice were unable to control bacterial proliferation and their spleen T cells were almost unresponsive in vitro to specific antigens of M. avium. Susceptibility of mice deficient in IL‐12 was similar to that of interferon‐γ (IFN‐γ)‐deficient mice. These data indicate a crucial role of IL‐12 in the development of a T‐cell population able to produce IFN‐γ and to mediate protection against M. avium infection. Treatment of M. avium‐infected mice with IL‐12 induced CD4+ T cells with enhanced capacity to produce IFN‐γ as well as to confer increased protection against M. avium.
Control of replication of plasmid R1: the duplex between the antisense RNA, CopA, and its target, CopT, is processed specifically in vivo and in vitro by RNase III.

The replication frequency of IncFII plasmids is regulated through the availability of a rate‐limiting protein, RepA. The synthesis of this protein is controlled post‐transcriptionally by a small antisense RNA, CopA, which binds to the leader region of the RepA mRNA (CopT). In this communication we report studies of the IncFII plasmid R1. We show that the duplex between CopA and CopT is cleaved specifically in vivo. The in vivo cleavage maps to the same position as that resulting from in vitro cleavage of a CopA/CopT duplex by purified RNase III. By introducing plasmids carrying translational repA‐lacZ fusions into cells deficient in RNase III we show that the expression of repA is elevated when RNase III activity is severely decreased. Hence, cleavage by RNase III seems to be a key event in the copy number control system of plasmid R1.
Metronomic Low Dose Leucovorin- Fluorouracil versus Supportive Treatment for Patients with Recurrent or Metastatic Colorectal Cancer

Introduction: There was an improvement in therapeutic regimens for advanced colorectal cancer (CRC) in the last few decades. The low dose metronomic palliative chemotherapy in patients with advanced CRC after the failure of standard chemotherapy led to a dramatic increase in efficacy, reduction of mortality rates, and improves survival in the form of control symptoms, and enhances or improves quality of life which is an important issue in that group of patients. Patients and Methods: We include 60 Patients with recurrent or metastatic colorectal cancer after failure of multiple lines of chemotherapy. The patients were randomized in two groups either to receive supportive treatment in group A (30 patients) or low dose weekly leucovorin 20 mg/m² plus 5-flourouracil 425 mg/m² for 3 weeks and 1 week rest in group B (30 patients). Patients in group B received palliative chemotherapy for 4 months at least. Results: After a follow up period of 19 months, the mean time to progression (TTP) is 4.9 months for the group (A) but is higher in group (B) as it is 7.8 months and it shows a statistically significant difference (P value <0.001). Also, the mean overall survival(OS) is 15.3 months for group (A) and 18.8 months for group (B) and this is statistically significant (P value <0.002). No grade 3 or 4 toxicity was detected. After 4 months of the study, 29 patients (96.6%) still have the stable disease compared to 18 patients (60%) of group (A). After 8 months, only 12 patients (40%) of group (B) show stable disease while all patients of group (A) have disease progression. Conclusion: We conclude that metronomic weekly leucovorin-5 FU could provide a good tolerable way to go on with chemotherapy treatment while at the same time not have major threatening side effects.
Faculty development in medical institutions: where do we stand in Pakistan?

BACKGROUND The term 'Faculty Development' encompasses all those activities which help faculty members enhance their academic competencies. It comprises three domains: personal development, professional development, and instructional and course development. The objectives of this study were to determine the proportion of medical colleges involved in faculty development activities, to assess the types of faculty development activities, and to identify the factors influencing such activities, along with formulating recommendations for faculty development. METHODS A cross-sectional study was conducted in the medical colleges (public and private) of Pakistan from September to December 2010. A questionnaire was designed through literature review, was pre-tested and then sent via mail to principals of the institutions outside Lahore. Questionnaires were self-administered to respondents within Lahore. Apart from describing the data, Chi-square and Fisher's exact tests were applied to determine statistical association between categorical variables at p < or = 0.05. RESULTS All the 65 public and private sector medical colleges recognised by the Pakistan Medical and Dental Council (PMDC) at that time were included in the study. Responses were received from 45 medical institutions, of which 37 (82%) were involved in faculty development activities. Training on communication skills were provided by 31 (84%), and teaching skills by 30 (81%) institutes. Stress management was the topic addressed by 15 (40%) institutes. Most institutes conducted such activities once a month (43%), followed by once every six months (30%). Faculty at all levels was equally involved in training activities, except senior registrars involved by 5 (14%). The presence of Medical Education Department (DME) in the college (p < 0.01), the respondent's designation (p = 0.0038) and the provincial location of the college (p = 0.036) were significantly associated with faculty development activities. The barriers to faculty training were identified as: lack of incentives 20 (54%), lack of faculty interest 15 (40%), and dearth of trained facilitators 15 (40%). CONCLUSION Majority of the medical institutes were involved in faculty development activities imparting training regarding communication and teaching skills. Presence of DME in the college, the respondent's designation, and the provincial location of the college positively influenced faculty development activities. Lack of incentives, lack of faculty interest and a shortage of trained faculty were identified as barriers.
Nitric oxide, lipid peroxidation and total thiol levels in acute appendicitis

Background: The mechanisms involved in the pathology of acute appendicitis (AA) and the factors affecting the progression have still been investigated. Oxidative stress is one of the factors of interest. Nitric oxide (NO) and its role in AA has not been studied previously. Methods: Thirty‐four patients who underwent operation with a perioperative diagnosis of AA and 16 age and sex‐matched controls were included in the study. Serum thiobarbituric acid reactive substances (TBARS), thiol groups (SH), NO metabolites (NOx), and conventional inflammation markers were determined. Results: NOx, TBARS, C‐reactive protein (CRP) levels, white blood cell (WBC) count, and erythrocyte sedimentation rate (ESR) were significantly higher, and total SH was significantly lower in AA than in control group. NOx, TBARS, and SH levels were comparable in acute phlegmonous appendicitis and advanced appendicitis. There was a significant positive correlation between NOx and TBARS, CRP, ESR, WBC and a significant negative correlation between NOx and SH. Conclusions: Serum NOx levels and oxidative stress elevate in AA independent from the extent of the lesion. Increased NO may play a role in the increased oxidative stress in AA. J. Clin. Lab. Anal. 24:63–66, 2010. © 2010 Wiley‐Liss, Inc.