Phylogenetic comparison of the HA-gene revealed a rather homogeneous cluster with other local isolates from recent years, the A36R-gene was mostly related to elephant derived strains from Germany. Despite

causing disease in human, the isolate AT/Carinthia/788/07 surprisingly even at high titers showed a highly reduced virulence in BALB/c mice upon intranasal inoculation as compared to vaccinia virus. This contrasts earlier reports on other CPXV isolates. Using shotgun DNA sequencing several insertions and deletions were found in genes presumably involved in host range, immune regulation as well as established virulence factors. These preliminary data could be an indication that CPXV strains with proven pathogenicity for humans may have reduced virulence

in mice and vice versa. Additionally strains with a reduced virulence may have an advantage in persisting in Fludarabine price less dense rodent populations. (C) 2011 Elsevier Ltd. All rights reserved.”
“We have investigated the microstructure and local chemistry of Ta/Ru/Ta/CoFeB/MgO/CoFeB/Ta/Ru magnetic tunnel junctions with different values of tunneling magnetoresistance (TMR) as a result of annealing at different temperatures. Annealing at 500 degrees C led to the templated crystallization of the amorphous CoFeB layer having coherent interfaces with MgO grains with an orientation relationship of < 001 >[011](MgO)parallel to < 001 >[001](CoFe), and the B rejected from crystallized CoFeB was found to be dissolved Selleck SHP099 in upper amorphous Ta layers and segregated in the bottom crystalline Ta layer. Annealing at 600 degrees C led to the dissolution of 3-4 at. % Ta in the MgO barrier, and B was found to be segregated at the CoFeB/MgO and Ta/Ru interfaces as a result of the crystallization of the top amorphous Ta layer. Further degradation in TMR of the samples annealed at 650 degrees C results from the loss of bcc-CoFe (001) texture in the bottom CoFeB electrode due to the pronounced Ta diffusion into the CoFe/MgO/CoFe layers. (C) 2009 American Institute of Physics. [DOI: 10.1063/1.3182817]“
“Organoclay was prepared

by a precipitation-adsorption process in which sodium-montmorillonite (Na-MMT) suspension was fully mixed Torin 1 inhibitor with an anionic surfactant, sodium dodecylbenzene sulfonate, and then precipitation agent CaCl(2) was added to produce a precipitate of organophilic montmorillonite (OMMT). The Na-MMT suspension was obtained by ion-exchange reaction of bentonite with sodium cation resin. Fourier transform infrared spectroscopy spectral analysis confirmed the adsorption of organic groups on the MMT, and the organic groups content was calculated from the results of thermal gravimetric analysis. X-ray diffraction results indicated that the OMMT prepared was exfoliated. In this article, the mechanism of the precipitation-adsorption process was discussed. (C) 2009 Wiley Periodicals, Inc.

“
“Protein-protein

interactions (PPIs) and multi-protein complexes perform central roles in the cellular systems of all living organisms. In humans, disruptions of the normal patterns of PPIs and protein complexes find more can be causative or indicative of a disease state. Recent developments in the biological applications of mass spectrometry (MS)-based proteomics have expanded the horizon for the application of systematic large-scale mapping of physical interactions to probe disease mechanisms. In this review, we examine the application of MS-based approaches for the experimental analysis of PPI networks and protein complexes, focusing on the different model systems (including human cells) used to study the molecular basis of common diseases such as

cancer, cardiomyopathies, diabetes, microbial infections, and genetic and neurodegenerative disorders.”
“Different melanocytic nevi have been reported as being associated with dermal cysts. Signet ring cell melanocytic nevus is a rare variant of melanocytic nevus characterized by cells with signet ring morphology within a common melanocytic nevus. This article describes an exceptional case of melanocytic nevus composed exclusively of signet ring cells over a trichilemmal cyst. Histologically, above the cyst, there was a small, symmetrical DAPT concentration and sharply demarcated lesion showing a compound proliferation of small, round, monomorphous cells with signet ring morphology. Immunohistochemically, signet ring cells were negative for cytokeratin AE1/3, leukocyte common antigen, HMB-45, and CD34. Occasionally, isolated signet ring cells were positive for

S-100 and melan A. Melanocytic nevus composed of signet ring cells should raise the differential diagnosis with other cutaneous tumors exhibiting signet ring cells. Previous cases Apoptosis inhibitor of this entity reported in the literature are also reviewed.”
“Purpose of review

To examine the occurrence and pathophysiology of vasculitis in rheumatoid arthritis (RA), describe the epidemiology and clinical features, and provide a therapeutic perspective.

Recent findings

With improved control of RA over the past two decades, the risk of severe outcomes such as vasculitis may be decreasing, Rheumatoid vasculitis continues to be associated with longstanding, erosive, seropositive disease, and it has recently been shown to be more frequent among patients with antibodies to cyclic citrullinated peptides. Apart from circulating immune complexes, expansion of cytotoxic CD28(null) T cells and circulating proinflammatory cytokines also play a role in the pathogenesis. The role of agents directed against the tumor necrosis factor (TNF) in the occurrence and management of rheumatoid vasculitis remains unclear, as rheumatoid vasculitis may be both associated with and treated with anti-TNF agents, once it has appeared.

Despite the increase in Status 1A and Status 1B recipients at transplant, posttransplant survival has continued

to improve. With the rise in infant candidates for transplantation and their high waiting list mortality, better means of supporting infants in need of transplant and allocation of organs to infant candidates is clearly needed.”
“P>Alloreactive NK cells (Allo-NKs) have been shown to exert advantageous effects on the outcomes of haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) for cancer treatment. However, the mechanisms of action of Allo-NKs remain unclear. We established a novel Haplo-HSCT conditioning regimen composed of Allo-NKs and a low Galardin molecular weight dose of immunosuppressive drugs (Allo-NKs + Chemo) to investigate alternative mechanisms besides direct cytotoxicity. The inhibitory effects of different cell subsets on the ATM Kinase Inhibitor donor-recipient mixed lymphocyte reactions (MLRs) were evaluated after Haplo-HSCT. The quantities and functions of CD4+CD25+ regulatory T cells (Tregs) and dendritic cells (DCs) in the spleen and the thymus were examined. Our results showed that the Allo-NKs + Chemo regimen induced systemic tolerance, and that CD4+CD25+ Tregs played a significant role in inducing and maintaining systemic tolerance after Haplo-HSCT.

Alloreactive NK cells promoted the expansion of recipient-derived CD4+CD25+CD127- Tregs in the thymus and the spleen which could click here be amplified in vitro by the immature donor-derived DC subset isolated from the thymus of Allo-NKs + Chemo-treated mice. Our findings suggested that Allo-NKs are capable of

inducing systemic tolerance after Haplo-HSCT by assembling donor-derived immature DCs to expand recipient-derived Treg cells in the thymus.”
“We report results for the surface morphological stability of a thin film that lies on a finite-thickness substrate and is subjected simultaneously to an external electric field. The film is grown epitaxially on the substrate and may undergo a Stranski-Krastanow instability due to its lattice mismatch with the substrate material. We develop a model for the surface morphological evolution of the thin film and conduct a linear stability analysis to examine the morphological stability of the epitaxial film’s planar surface state. Our analysis shows that surface electromigration due to a properly applied and sufficiently strong electric field can inhibit Stranski-Krastanow-type instabilities, which can be used to control the onset of island formation on the film surface. We find that using a finite-thickness substrate can have the beneficial effect of reducing the critical strength of the electric field required to stabilize the planar surface morphology of the epitaxial film with respect to the field strength required in the case of an infinitely thick substrate.

Urethral samples were obtained using a swab inserted 3-4 cm into the urethral KPT-8602 solubility dmso meatus. Ureaplasma urealyticum and Mycoplasma hominis were detected by the kit Mycofast R evolution 3 Elitech Microbiology (Elitech Microbiology, Signes, France). Ureaplasma urealyticum was detected in 15.6% of the cases and Mycoplasma hominis in 3.6%. One patients had a co-infection with both pathogens. About 41% of the infertile patients with mycoplasma infection had urogenital symptoms. A lower number of patients with mycoplasma infection had normal sperm parameters compared with non-infected infertile men, but this frequency showed only a trend compared to non-infected patients (Chi-square=3.61;

P=0.057), and a significantly higher percentage of patients with oligo-astheno-teratozoospermia (Chi-square=127.3; P<0.0001), or asthenozoospermia alone (Chi-square=5.74; P<0.05) compared to non-infected infertile patients. In conclusion, this study showed an elevated prevalence of ureaplasma urealyticum and mycoplasma hominis infection find more in unselected men attending an infertility outpatient clinic and that the presence of these microorganisms is associated with a higher percentage of patients with abnormal sperm parameters.”
“In

cells, anthocyanin pigments are synthesized at the cytoplasmic surface of the endoplasmic reticulum, and are then transported and finally accumulated inside the vacuole. In Vitis vinifera (grapevine), two kinds of molecular actors are putatively associated with the vacuolar sequestration of anthocyanins: a glutathione-S-transferase

(GST) and two MATE-type transporters, named anthoMATEs. However, the sequence of events by which anthocyanins are imported into the vacuole remains unclear. We used MYBA1 transformed hairy roots as a grapevine model tissue producing anthocyanins, and took advantage of the unique autofluorescence of anthocyanins to study their cellular trafficking. In these tissues, anthocyanins were not only visible in the largest vacuoles, but were also present at higher concentrations in several vesicles of different sizes. In the cell, small vesicles actively moved alongside learn more the tonoplast, suggesting a vesicular trafficking to the vacuole. Subcellular localization assays revealed that anthoMATE transporters were closely related with these small vesicles, whereas GST was localized in the cytoplasm around the nucleus, suggesting an association with the endoplasmic reticulum. Furthermore, cells in hairy roots expressing anthoMATE antisense did not display small vesicles filled with anthocyanins, whereas in hairy roots expressing GST antisense, anthocyanins were accumulated in vesicles but not in the vacuole. This suggests that in grapevine, anthoMATE transporters and GST are involved in different anthocyanin transport mechanisms.

The epigenome is particularly susceptible to deregulation during early embryonic and neonatal periods and thus disturbances during these periods can have latent

lasting effects. The Latent Early-life Associated Regulation (LEARn) model attempts to explain these consequences selleck from a brain specific point of view. In the present review we present the evidence that support the role of epigenetics in the development of AD and explore the potential pathways and mechanisms that may be involved.”
“Background: Roll Back Malaria (RBM) interventions such as insecticide-treated mosquito nets (ITN) and artemisinin-based combination therapy (ACT) have become implemented with different

velocities in the endemic countries of sub-Saharan Africa (SSA) in recent years. There is conflicting evidence on how much can be achieved under real life conditions with the current interventions in the highly endemic savannah areas of SSA.

Methods: The study took place in a rural area of north-western Burkina Faso, which was defined as holoendemic in 1999. Clinical and parasitological data were compared in two cohorts of young children of the same age range from eight villages. Surveys took place in June and December of the year 1999 and 2009 respectively.

Results: Prevalence of mosquito net use increased from 22% in 1999 to 73% in ATR inhibitor 2009, with the majority of nets being ITNs in 2009. In 2009, P. falciparum SNS-032 prevalence was significantly

lower compared to 1999 (overall reduction of 22.8%).

Conclusions: The reduction in malaria prevalence in young children observed between 1999 and 2009 in a rural and formerly malaria holoendemic area of Burkina Faso is likely attributable to the increase in ITN availability and utilization over time.”
“Background. A 5-year-old white girl with a history of hypothyroidism in infancy presented to the endocrinology clinic of a tertiary hospital. Her physical examination noted a stocky physique, broad chest, short neck and short digits. two years later, skin examination revealed subcutaneous nodules and acanthosis nigricans.

Investigations. Measurement of levels of serum phosphate, parathyroid hormone, ionized calcium and insulin; measurement of peak growth hormone by the arginine-levodopa stimulation test; calculation of homeostasis model assessment of insulin resistance; assessment of bone age; DNA analysis of the GNAS gene.

Diagnosis. Pseudohypoparathyroidism type 1a in a patient with Albright hereditary osteodystrophy, characterized by hypocalcemia, hypothyroidism, growth-hormone deficiency and insulin resistance.

Management.

Symptoms were evaluated by a validated questionnaire and anatomy by pelvic organ prolapse quantification (POPQ).

Significant more cases, 97% versus 81% controls, felt cured Quisinostat datasheet or much improved (p = 0.02); 11% of cases and 19% of controls had

POP symptoms, POPQ > -1 was found in 31% cases and 24% controls. Defining recurrence as POPQ > -1 plus symptoms revealed recurrence in 3% of cases and 12% controls. None of the recurrence rates was significantly different for cases versus controls. No vaginal erosions were seen. Previous surgery was a significant risk factor with odds ratio 7.3 for another recurrence.

Recurrence rates defined by POPQ plus symptoms were low compared to literature. Xenograft reinforcement might improve results.”
“Ultrafast time-domain electro-optical characterization of the ballistic three-branch junctions (TBJs) has been performed to investigate their electrical response at terahertz (THz)

frequencies. check details A TBJ rectifier consisting of two TBJs in parallel was placed in a coplanar waveguide (CPW) in which subpicosecond electrical pulses were generated by a photoconductive switch. A LiTaO3-based electro-optic transducer measured the waveform of the incident and transmitted voltage signals with a subpicosecond temporal resolution. This experimental configuration allowed the rectifier’s electrical response to be studied with a bandwidth of up to 1 THz. Detailed analysis of the TBJ rectifier and the photoconductive switch was performed in both

the time domain and frequency domain. This analysis revealed poor coupling of the excitation signal into the rectifier because of a severe impedance mismatch between the rectifier and CPW as well as a parasitic capacitive coupling between the input and output ports of the rectifier. The poor coupling limited our ability to observe any substantial nonlinear response of the rectifier at THz frequencies. Possible solutions for enhancing the system bandwidth and efficient THz rectification are presented. c Epigenetic inhibitor purchase 2010 American Institute of Physics. [doi: 10.1063/1.3330742]“
“Diffuse cavernous hemangioma of the uterus in pregnant woman is an extremely rare condition. A total of eight cases have been described in the literature till date. The antenatal diagnosis as well as management requires considerable skill. Although it is a benign condition but it can have serious consequences for the mother as well as the baby.

Here we describe an interesting case of diffuse cavernous hemangioma of the uterus in a 21-year-old G3, P2-0-0 pregnant woman, who underwent hysterectomy for uncontrollable bleeding during third cesarean section. The diagnosis of diffuse cavernous hemangioma was made only on histopathological examination of the hysterectomy specimen.

Diffuse hemangioma of the uterus in a pregnant woman is a serious condition, which may not be detected early during the pregnancy. This can result in uncontrolled bleeding especially during operative delivery and may require hysterectomy.

“
“It is not clear whether antipseudomonal agents Chk inhibitor can kill cell-associated bacteria within a short time. Madin-Darby canine kidney (MDCK) and A549 cells were infected with Pseudomonas aeruginosa ATCC 27853 and PAO1 and the bactericidal activity of ceftazidime, imipenem, meropenem, gentamicin, and ciprofloxacin against the organisms was investigated. In both MDCK and A549 cells, beta-lactams could not kill epithelial cell-associated bacteria within 2 h. Gentamicin at concentrations a parts per

thousand currency sign32 mu g/ml killed more than 99% of epithelial cell-associated bacteria. Ciprofloxacin at 0.5 mu g/ml killed more than 99.9% of MDCK cell-associated bacteria. Ciprofloxacin has the strongest and most rapid bactericidal activity against epithelial cell-associated bacteria, which may be explained by the combination of potent in-vitro bactericidal activity and high penetration ability into epithelial cells.”
“Purpose: To investigate the antimicrobial activity of crude and fractionated extracts of Biemna tubulosa and Stylissa spp. thriving in Trou aux Biches lagoon, North East Mauritius.

Methods: Crude extracts (methanol: dichloromethane 1: 1) and fractions of Biemna tubulosa and Stylissa spp (hexane, ethyl acetate and butanol)

were tested against some bacterial organisms, namely, Escherichia coli, Staphylococcus aureus and Enterococcus faecalis, using broth microdilution assay. The extracts were screened for the presence of compounds that could be responsible for bioactivity.

Results: Preliminary chemical screening revealed the presence of tannins, saponins, terpenes, alkaloids and phenols. Cell Cycle inhibitor The hexane fraction of Stylissa spp. and the ethyl actetate and butanol extracts of Biemna tubulosa were more active than the control antibiotic. Maximum antimicrobial activity was noted for the butanol fraction of Biemna tubulosa with minimum inhibitory concentration (MIC)

of 0.091 mg/ml against E. coli. The hexane soluble fraction of Stylissa spp. was more active with MIC of 0.125 mg/ml against S. aureus and E. coli and 0.250 mg/ml against E. faecalis.

Conclusion: The broad selleck screening library spectrum antibacterial activity of these sponges seemed to be due to the presence of sesterterpenes and triterpenes, alkaloids and tannins detected in the extract fractions. This is probably the first report on the antimicrobial activity of Biemna tubulosa and Stylissa spp. from Mauritius waters.”
“Rupture of the upper ankle joint ligaments is a common injury. Therapy in patients with Ehlers Danlos Syndrome (EDS) is a challenge due to the autosomal-dominant collagenopathy. Therapeutic recommendations and long term results in treatment of patients with EDS are rare. Therefore uncertainty exists. We present a case of clinical and radiologic long term results after ligament rupture of the upper ankle joint in a patient with EDS.

Increasing sensitivity will be of benefit in compensating for the relatively low power of current high resolution continuous wave THz radiation techniques, and to fully express the potential of THz spectroscopy as source power increases. Improved sensitivities, and thus scanning speeds, will allow detailed studies of the complex vibration-rotation-tunneling

Citarinostat order dynamics that large molecules show at THz wavelengths, and will be especially important in studying more elusive, transient species such as those present in planetary atmospheres and the interstellar medium. Coupling radiation into the cavity presents unique challenges at THz frequencies, however, meaning that the cavity configurations common in neighboring frequency domains cannot simply be translated. Instead, novel constructions are needed. Here we present a resonator design in which wire-grid polarizers serve as the input and output coupling mirrors. Using this configuration, Q-factors of a few times 10(5) are achieved near 0.3 THz. To aid future investigations, the parameter space that limits the quality of the cavity is explored and paths to improved performance highlighted. Lastly, the performance of polarizer cavity-based Fourier transform (FT)

THz spectrometers is discussed, in particular those design optimizations that should allow for the construction of THz instrumentation this website that rivals and eventually surpasses the sensitivities achieved with modern FT-microwave cavity spectrometers. (C) 2011 American Institute of Physics. [doi:10.1063/1.3560771]“
“Objectives: The aim of this study was to evaluate the effect of the G3057A (rs62589000) LEPR polymorphism on obesity risk

and plasma leptin, insulin, and lipid levels in a sample of the Tunisian population.

Design and methods: Three hundred and ninety-three obese patients and 317 controls participated in this study. The G3057A genotype was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.

Results: In the entire study sample, no significant differences in HDAC inhibitor genotype frequencies were observed between obese patients and controls. However, stratified analysis by gender revealed a quantitative increase in the variant allele (33.3% vs. 25.8%; chi(2) = 4.90, p = 0.026) in obese women (but not men) compared to controls. When a dominant model of inheritance was assumed, the GA + AA genotypes were more prevalent in these obese female patients than in controls (58.3% vs. 47.8%; chi(2) = 4.08, p = 0.044). Unconditional logistic regression showed that in women only, obesity risk was significantly higher for homozygotes for the variant allele (OR = 2.73, 95% CI 1.03-7.21) and for carriers of GA + AA genotypes (OR=1.53, 95% CI 1.01-2.31) compared with homozygotes for the normal allele. The association between the G3057A LEPR variant and obesity remained statistically significant even after adjustment for age.

More than 90% of the patients achieved stable analgesic dose within 3 days. After using SR oxycodone tablets for 1 week, sleep quality was significantly (P < 0.01) improved. In week 1, the average dose of SR oxycodone tablets was 16.63 +/- 7.79 mg.

The average daily dose of most patients was about 20 mg after 2 weeks. In all the enrolled patients, 38 (47.5%) had adverse reactions. No serious adverse reactions took place.

Conclusion. The results of this clinical observation further elaborated the efficacy and safety of SR oxycodone tablets in the treatment of moderate to severe painful diabetic peripheral neuropathy in China.”
“Objective-To determine the prevalence of lymphoplasmacytic synovitis (LPS) in dogs with naturally occurring cranial cruciate ligament (CCL) rupture and compare BMS-777607 molecular weight clinical, radiographic, cytologic, and histologic findings in dogs with and without LPS.

Design-Cross-sectional study.

Animals-110 dogs with naturally occurring CCL rupture.

Procedures-Histologic examination of synovial biopsy specimens obtained at the AZD1208 JAK/STAT inhibitor time of surgical treatment was used to identify dogs with LPS. Clinical, radiographic, cytologic, and histologic findings were compared between

dogs with and without LPS.

Results-56 (51%) dogs had histologic evidence of LPS. There were no significant differences in age, body weight, duration of lameness, severity of lameness, severity of radiographic signs of degenerative joint disease, extent of CCL rupture (partial vs complete), or gross appearance of the medial meniscus between dogs with and without LPS. Mean tibial plateau angle was significantly lower in dogs with LPS than in dogs without LPS, and dogs with LPS were significantly more likely to have neutrophils in their synovial fluid. Lymphocytes were seen in synovial fluid from a single dog with LPS.

Conclusions and Clinical Relevance-Results suggested that LPS was common in dogs with naturally occurring CCL rupture. However,

only minor clinical, radiographic, cytologic, and histologic differences were identified between dogs with and without LPS. (J Am Vet Med Assoc 2009;235:386-390)”
“Protein-protein FG-4592 Angiogenesis inhibitor interaction networks (PPINs) are a powerful tool to study biological processes in living cells. In this review, we present the progress of PPIN studies from abstract to more detailed representations. We will focus on 3D interactome networks, which offer detailed information at the atomic level. This information can be exploited in understanding not only the underlying cellular mechanisms, but also how human variants and disease-causing mutations affect protein functions and complexes’ stability. Recent studies have used structural information on PPINs to also understand the molecular mechanisms of binding partner selection. We will address the challenges in generating 3D PPINs due to the restricted number of solved protein structures.

The W/O/W multiple emulsion containing NTX hydrochloride may represent a potential alternative dosage form for the treatment of alcohol dependence.”
“While myriad molecular formats selleck compound for bispecific antibodies have been examined to date, the simplest

structures are often based on the scFv. Issues with stability and manufacturability in scFv-based bispecific molecules, however, have been a significant hindrance to their development, particularly for high-concentration, stable formulations that allow subcutaneous delivery. Our aim was to generate a tetravalent bispecific molecule targeting two inflammatory mediators for synergistic immune modulation. We focused on an scFv-Fc-scFv format, with a flexible (A(4)T)(3) linker coupling an additional scFv to the C-terminus of an scFv-Fc. While one of the lead scFvs isolated directly from a naive library was well-behaved and sufficiently potent, the parental anti-CXCL13 scFv 3B4 required optimization for affinity, stability, and cynomolgus ortholog cross-reactivity. To achieve this, we eschewed framework-based stabilizing ZD1839 mutations in favor of complementarity-determining region (CDR) mutagenesis and re-selection for simultaneous improvements in both affinity and thermal stability.

Phage-displayed 3B4 CDR-mutant libraries were used in an aggressive hammer-hug selection strategy that incorporated thermal challenge, functional, and biophysical screening. This approach identified leads with improved stability and >18-fold, and 4,100-fold higher Crenigacestat affinity

for both human and cynomolgus CXCL13, respectively. Improvements were exclusively mediated through only 4 mutations in V-L-CDR3. Lead scFvs were reformatted into scFv-Fc-scFvs and their biophysical properties ranked. Our final candidate could be formulated in a standard biopharmaceutical platform buffer at 100 mg/ml with <2% high molecular weight species present after 7 weeks at 4 degrees C and viscosity <15 cP. This workflow has facilitated the identification of a truly manufacturable scFv-based bispecific therapeutic suitable for subcutaneous administration.”
“Preparation of new hetaryl-containing planar chiral ferrocene by a nucleophilic substitution of hydrogen in azines was performed using a lithium derivative of (S)-ferrocenyl-p-tolylsulfoxide as s nucleophilic reagent.”
“Antibody interactions with Fc receptors (FcRs), like FcRIIIA, play a critical role in mediating antibody effector functions and thereby contribute significantly to the biologic and therapeutic activity of antibodies. Over the past decade, considerable work has been directed towards production of antibodies with altered binding affinity to FcRs and evaluation of how the alterations modulate their therapeutic activity. This has been achieved by altering glycosylation status at N297 or by engineering modifications in the crystallizable fragment (Fc) region.